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1
Ostry, Sylvia. "Comparative Research Approaches." Relations industrielles 21, no. 4 (2005): 511–17. http://dx.doi.org/10.7202/027728ar.
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In the minds of many people, the Dominion Bureau of Statistics appears as a kind of factory producing data. It is more than that. This paper shows that the Bureau is taking new leads in the field of developmental and analytical research bearing on revised and new statistical series.
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Ruggles, Steven, Catherine Fitch, Diana Magnuson, and Jonathan Schroeder. "Differential Privacy and Census Data: Implications for Social and Economic Research." AEA Papers and Proceedings 109 (May 1, 2019): 403–8. http://dx.doi.org/10.1257/pandp.20191107.
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The Census Bureau has announced new methods for disclosure control in public use data products. The new approach, known as differential privacy, represents a radical departure from current practice. In its pure form, differential privacy techniques may make the release of useful microdata impossible and limit the utility of tabular small-area data. Adoption of differential privacy will have far-reaching consequences for research. It is likely that scientists, planners, and the public will lose the free access we have enjoyed for six decades to reliable public Census Bureau data describing US social and economic change.
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Kuhnl, Andrea, Claire Roddie, Nuria Martinez-Cibrian, et al. "Real-World Data of High-Grade Lymphoma Patients Treated with CD19 CAR-T in England." Blood 134, Supplement_1 (2019): 767. http://dx.doi.org/10.1182/blood-2019-124177.
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Background After European Medicines Agency (EMA) approval of axicabtagene ciloleucel and tisagenlecleucel for the treatment of relapsed/refractory (r/r) high-grade lymphoma in 2018, England was one of the first European countries granting fully funded access to these CD19 CAR-T therapies. Both products are available through the National Health Service England (NHSE) Cancer Drug Fund until their cost-effectiveness has been determined. The NHSE CAR-T program has been set up in a structure aiming to implement robust and transparent criteria for patient selection and to ensure equity of treatment access: CAR-T slots are approved by a weekly National CAR-T Clinical Panel (NCCP), consisting of independent clinical experts, patient representatives, and delegates from each CAR-T centre; treatment is delivered in 7 geographically spread commissioned CAR-T centres (Birmingham, Bristol, King's College Hospital London, University Hospital London, The Christie Manchester, Manchester Royal Infirmary, Newcastle). Here, we report prospective data on the first 122 lymphoma patients approved by the NCCP. Methods Patients with r/r high-grade lymphoma referred to the NCCP between December 2018 and July 2019 and deemed eligible for treatment with CD19 CAR-T were analysed. Eligibility was assessed in the CAR-T centre's tumor board, based on organ function and fitness (performance status 0/1), absence of active CNS disease, and biopsy confirmation of r/r high-grade lymphoma. The final decision on patient eligibility was made by consensus through the NCCP independent clinical panel. CAR-T product selection for each patient was done by the CAR-T centre, mainly on the basis of manufacturing slot availability. Results 122 patients were approved for treatment with CD19 CAR-T therapy by the panel. CAR-T centres selected 76 patients for axicabtagene ciloleucel and 46 for tisagenlecleucel. Patients' median age was 56 years (range 18-75). 62% were male. 87 (71%) patients had de novo diffuse large B-cell lymphoma, 29 (24%) transformed lymphoma (23 from follicular- and 6 from marginal zone lymphoma), and 6 (5%) primary mediastinal B-cell lymphoma. 96 (79%) patients had biopsy confirmation of disease prior to submission. 71 (58%) patients had received 2 prior lines of therapy for high-grade lymphoma, 51 (42%) patients 3 or more treatment lines (maximum 6). 5 patients had previous allogeneic, 19 previous autologous transplant. 88% of patients (107/122) were refractory to the last line of treatment (stable- or progressive disease (PD) or relapse within 6 months). Among 122 patients, 112 completed leukapheresis, 3 are awaiting the procedure, and 7 patients did not proceed (6 due to PD, 1 opted for radical radiotherapy). 57 of 112 patients were infused at the time of abstract submission, 42 are awaiting CAR-T infusion. 10 patients did not proceed to infusion due to disease progression and clinical deterioration (3 with CNS relapse), 2 due to manufacturing failure. One patient achieved a complete response following bridging therapy and is currently monitored. 84% (88/105) patients received bridging therapy between the time of NCCP approval and CAR-T infusion (median 64 days), 62 had chemotherapy, 9 radiotherapy, and 17 steroids only. Details on bridging therapy, treatment-related toxicities and outcomes will be provided at the meeting, by which time approximately 62 patients will have completed their 3 months PET response assessment. Conclusion NHSE has successfully implemented a national structure for providing licenced CAR-T products in England, enabling equity of access and oversight on capacity and patient outcomes, which can serve as a model for newly licenced, cost-intense and complex cell- and gene therapies in the future. The prospective and centralised nature of this dataset offers a true reflection of the real-world patient population undergoing CAR-T therapy in England. Disclosures Kuhnl: Kite Gilead: Honoraria. Roddie:Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy. Menne:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Kyowa Kirin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau. Sanderson:Kite/Gilead: Honoraria. Osborne:Novartis: Other: Travel; Pfizer: Honoraria, Speakers Bureau; MSD: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Speakers Bureau; Servier: Consultancy; Gilead: Consultancy. Radford:AstraZeneca: Equity Ownership, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Research Funding; GSK: Equity Ownership; Seattle Genetics: Consultancy, Honoraria. Patten:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Roche: Honoraria, Research Funding. O'Reilly:Kite Gilead: Honoraria. Bloor:Abvie, Gilead, Novartis, Autolus, Celgene, etc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational grant. Rowntree:Novartis: Consultancy. Bowles:Abbvie: Research Funding; Janssen: Research Funding. Collins:Gilead: Consultancy, Honoraria. McMillan:BMS: Honoraria; Celgene: Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Gilead: Honoraria; Novartis: Honoraria; Sandoz: Honoraria; Pfizer: Honoraria, Research Funding; MSD: Honoraria.
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Yang, Junda, Yun Xia, Liu Yang, and Zhongtao Zhang. "Research on “First-Class” Financial Management of Power Grid Enterprises Based on IPA: Taking XX Power Supply Bureau as an Example." Journal of Management and Sustainability 8, no. 4 (2018): 74. http://dx.doi.org/10.5539/jms.v8n4p74.
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Using the data collected by the questionnaire survey, this paper uses IPA (importance performance analysis) to analyze the financial performance and operation status of some financial data of the XX power supply bureau, and finds the indicators that need to maintain the advantages and the indicators that need to be improved. It can provide reference for the construction of power supply bureaus and power companies to create first-class indicators.
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Miesbach, Wolfgang A., Giovanni Di Minno, Elena Santagostino, et al. "Efficacy and Safety of BAY 94-9027 (Damoctocog Alfa Pegol) Prophylaxis in Patients with Severe Hemophilia a and Comorbidities: A Post Hoc Analysis of PROTECT VIII Data." Blood 134, Supplement_1 (2019): 1117. http://dx.doi.org/10.1182/blood-2019-128486.
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Background: The availability of factor (F)VIII replacement products has dramatically improved life expectancy for patients with hemophilia A (HA). However, older patients face distinct challenges. Age-related comorbidities such as cardiovascular disease (CVD), often involving treatments that can increase the risk of bleeding, and patients who received treatment before the advent of recombinant products, are more likely to have been exposed to blood-borne viruses carrying chronic infections. It is important to understand clinical outcomes with FVIII products in patients with HA and these comorbidities. BAY 94-9027 (damoctocog alfa pegol; Jivi) is a B-domain deleted recombinant FVIII, site-specifically PEGylated with a 60 kDa (2×30 kDa) polyethylene glycol to extend its half-life. Efficacy and safety of BAY 94-9027 as prophylactic and on-demand therapy for patients with severe HA were demonstrated in the phase II/III PROTECT VIII trial and its Extension. This post hoc analysis assessed bleeding rates and safety outcomes for prophylaxis patients in PROTECT VIII and its Extension, based on the presence or absence of comorbidities of interest. Patients/Methods: PROTECT VIII (NCT01580293) was a partially randomized, open-label trial of 134 males aged 12-65 years with severe HA (FVIII <1%) and ≥150 FVIII exposure days. Prophylaxis patients (n=114) received BAY 94-9027 25 IU/kg twice weekly (2×W) for a 10-week run-in period. Patients with ≤1 spontaneous joint or muscle bleed during this period were randomized to 45-60 IU/kg every 5 days or 60 IU/kg every 7 days for the main 26-week study; patients enrolling after the randomization arms were full, or with ≥2 bleeds in the run-in period, received 30-40 IU/kg 2×W. Patients completing the main study could enter an extension, continuing BAY 94-9027 on any regimen used in the main study. Baseline characteristics, annualized bleeding rates (ABR) and safety were examined for patients on prophylaxis treatment during main study and its Extension with and without comorbidities of interest. Comorbidities included human immunodeficiency virus (HIV) infection, hepatitis B or C infection (HBV or HCV), and risk factors for CVD (hypertension, hypercholesterolemia, hypertriglyceridemia and hyperlipidemia). Results: A total of 104 patients who received BAY 94-9027 prophylaxis during the main study and the Extension (data cut-off: Jan 2018) were included in this analysis. Mean (SD) age of patients was 34.3 (13.0) years with a median (Q1;Q3) of 7 (2;15) bleeds in the 12 months before enrolment. Most patients (72.1%) had target joint(s) at baseline. Before study, 22 (21.2%) patients were receiving on-demand treatment; the remaining 82 were on regular prophylaxis. Most patients (n=66, 63.5%) had ≥1 comorbidity of interest. Of those, chronic HCV infection (HCV detection, asymptomatic) was most common (40/66, 60.6%), followed by acute HCV infection (HCV detection, symptomatic, 26/66, 39.4%), HBV infection (20/66, 30.3%), hypertension (17/66, 25.8%), hyperlipidemia (7/66, 10.6%), HIV infection (5/66, 7.6%), and hypertriglyceridemia (2/66, 3.0%). Patients with comorbidities of interest were older (mean age: 41.5 vs 21.9 years, respectively) and had a higher median (Q1;Q3) number of joint bleeds in the previous 12 months (5 [1;12] vs 3 [0;10], respectively) than patients without comorbidities (n=38). Pre-study, median ABR was 6.0 and 7.0 in patients with and without comorbidities of interest respectively, which decreased to 2.9 and 1.5 respectively during the main study, and further to 1.8 and 1.2 respectively during the Extension (Figure). In all patients with comorbidities of interest, robust improvements in median ABR were observed between the 12-month pre-study period and the main study period, and were maintained or improved in the Extension. Patients with comorbidities of interest had similar numbers of drug-related adverse events (AEs; 10.6% vs 23.7%), serious AEs (39.4% vs 28.9%) and discontinuations due to AEs (1.5% vs 2.6%) than those without comorbidities of interest during main study and Extension. Conclusions: The majority of patients (63.5%) in PROTECT VIII had ≥1 comorbidity of interest. The results from this post hoc analysis indicate that long-term BAY 94-9027 prophylaxis provided excellent control of bleed rates and was well tolerated in patients with severe HA and comorbidities of interest: HIV, HBV or HCV infection or risk factors for CVD. Figure Disclosures Miesbach: Biotest: Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria; Freeline: Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Research Funding, Speakers Bureau; Grifols: Speakers Bureau; Biomarin: Consultancy, Honoraria; LFB: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; UniQure: Consultancy, Honoraria, Research Funding; CSL: Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Bayer: Research Funding, Speakers Bureau; Octapharma: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau. Di Minno:Sanofi: Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Kedrion: Speakers Bureau; CSL: Speakers Bureau; Pfizer: Speakers Bureau; Novo Nordisk: Speakers Bureau. Santagostino:Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Spark: Speakers Bureau; Kedrion: Consultancy, Speakers Bureau; Bioverativ: Consultancy, Speakers Bureau; UniQure: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; CSL: Consultancy, Speakers Bureau; Sanofi: Speakers Bureau. Klamroth:Bayer, Biomarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, SOBI, Takeda: Consultancy; Bayer, Novo Nordisk, SOBI: Research Funding. Bayh:Bayer: Employment. Soto:Bayer: Employment. Hermans:LFB: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Octapharma: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria, Speakers Bureau; CAF-DCF: Consultancy, Honoraria, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; CSL: Consultancy, Honoraria, Speakers Bureau; Sobi: Consultancy, Honoraria, Speakers Bureau; Kedrion: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau.
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Courvoisier, D., K. Lauper, S. A. Bergstra, et al. "OP0199 POINTS TO CONSIDER WHEN ANALYSING AND REPORTING COMPARATIVE EFFECTIVENESS RESEARCH WITH OBSERVATIONAL DATA IN RHEUMATOLOGY." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 124–25. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1162.
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Background:Comparing drug effectiveness in observational settings is hampered by several major threats, among them confounding and attrition bias bias (patients who stop treatment no longer contribute information, which may overestimate true drug effectiveness).Objectives:To present points to consider (PtC) when analysing and reporting comparative effectiveness with observational data in rheumatology (EULAR-funded taskforce).Methods:The task force comprises 18 experts: epidemiologists, statisticians, rheumatologists, patients, and health professionals.Results:A systematic literature review of methods currently used for comparative effectiveness research in rheumatology and a statistical simulation study were used to inform the PtC (table). Overarching principles focused on defining treatment effectiveness and promoting robust and transparent epidemiological and statistical methods increase the trustworthiness of the results.Points to considerReporting of comparative effectiveness observational studies must follow the STROBE guidelinesAuthors should prepare a statistical analysis plan in advanceTo provide a more complete picture of effectiveness, several outcomes across multiple health domains should be comparedLost to follow-up from the study sample must be reported by the exposure of interestThe proportion of patients who stop and/or change therapy over time, as well as the reasons for treatment discontinuation must be reportedCovariates should be chosen based on subject matter knowledge and model selection should be justifiedThe study baseline should be at treatment initiation and a description of how covariate measurements relate to baseline should be includedThe analysis should be based on all patients starting a treatment and not limited to patients remaining on treatment at a certain time pointWhen treatment discontinuation occurs before the time of outcome assessment, this attrition should be taken into account in the analysis.Sensitivity analyses should be undertaken to explore the influence of assumptions related to missingness, particularly in case of attritionConclusion:The increased use of real-world comparative effectiveness studies makes it imperative to reduce divergent or contradictory results due to biases. Having clear recommendations for the analysis and reporting of these studies should promote agreement of observational studies, and improve studies’ trustworthiness, which may also facilitate meta-analysis of observational data.Disclosure of Interests:Delphine Courvoisier: None declared, Kim Lauper: None declared, Sytske Anne Bergstra: None declared, Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Thomas Frisell: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Joanna KEDRA: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Tanja Stamm Grant/research support from: AbbVie, Roche, Consultant of: AbbVie, Sanofi Genzyme, Speakers bureau: AbbVie, Roche, Sanofi, Simon Stones Consultant of: I have been a paid consultant for Envision Pharma Group and Parexel. This does not relate to this abstract., Speakers bureau: I have been a paid speaker for Actelion and Janssen. These do not relate to this abstract., Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific
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Hézode, Christophe, Michael W. Fried, Massimo Colombo, et al. "Efficacy and Safety of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Virus Infection and Inherited Blood Disorders: Final Data from the C-Edge Ibld Study." Blood 128, no. 22 (2016): 1303. http://dx.doi.org/10.1182/blood.v128.22.1303.1303.
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Abstract Background: Complications from chronic hepatitis C virus (HCV) infection are a major cause of morbidity and mortality among individuals with inherited blood disorders (IBLD). Inability to tolerate ribavirin and frequent comorbidities have limited HCV treatment options in these patients. The aim of the C-EDGE IBLD study was to evaluate the efficacy and safety of a once-daily, fixed-dose combination of elbasvir 50 mg (EBR, an NS5A inhibitor) and grazoprevir 100 mg (GZR, an NS3/4A protease inhibitor) in patients with HCV infection and IBLD, including those with hemoglobinopathies. Methods: C-EDGE-IBLD was a randomized, double-blind, placebo-controlled study of treatment-naïve and treatment-experienced patients with HCV genotype (GT)1, 4, or 6 infection and IBLD (hemophilia A/B, von Willebrand disease, β-thalassemia, or sickle cell anemia). Patients were randomized in a 2:1 ratio to an immediate-treatment group (ITG; 12 weeks of EBR/GZR) or deferred-treatment group (DTG; 12 weeks of placebo, followed by EBR/GZR for 12 weeks). Randomization was stratified according to the presence of cirrhosis and IBLD diagnosis. The primary endpoints were the proportion of patients in the ITG who achieved sustained virologic response (SVR12, HCV RNA <15 IU/mL 12 weeks after completion of treatment) and a comparison of safety and tolerability between patients receiving EBR/GZR in the ITG vs those receiving placebo in the DTG. Results: One hundred fifty-nine patients were randomized (ITG, n = 107; DTG, n = 52). Three patients in the DTG did not commence deferred active treatment; therefore, 156 patients received ≥1 dose of EBR/GZR. Mean age was 44 years. Other baseline patient demographics were as follows: 75% male; 18% black; 41% GT1a-infected; 46% GT1b-infected; 11% GT4-infected; 24% cirrhotic; 6% HIV/HCV co-infected; 43% with hemophilia A/B or von Willebrand disease; 38% with β-thalassemia; 18% with sickle cell anemia. SVR12 was achieved by 92.9% (145/156) of patients receiving EBR/GZR (ITG 93.5% [100/107]; DTG 91.8% [45/49]). Of the 11 patients who did not achieve SVR12, 2 discontinued treatment for reasons unrelated to study medication and 9 relapsed, including 7 who had NS5A resistance-associated variants present at baseline. One patient achieved SVR12 but relapsed between follow-up weeks 12 and 24. SVR12 was achieved by 90.8% (59/65), 95.7% (67/70), and 94.4% (17/18) of patients with HCV GT1a, GT1b, and GT4 infection, respectively (2 patients with GT1 non-a,b achieved SVR and the 1 patient with GT6 infection relapsed). SVR 12 was achieved by 96.3% (26/27) of patients with sickle cell anemia, 95% (57/60) with β-thalassemia, and 89.9% (62/69) with hemophilia A/B or von Willebrand disease. During the initial treatment period (EBR/GZR vs placebo), serious adverse events were reported in 3 (2.9%) patients in the ITG (1 drug-related, 2 related to IBLD) and 6 (11.5%) patients receiving placebo in the DTG (1 drug-related, 3 related to IBLD). In the DTG placebo phase, 1 patient discontinued treatment due to an adverse event and 1 patient withdrew consent. No patient in either arm discontinued treatment due to worsening of underlying IBLD. There was 1 hepatic event of clinical interest in each arm (ALT >3× baseline and >100 U/L). In the EBR/GZR treatment phase of the DTG (n = 49), 3 patients reported serious adverse events; none were drug-related and 2 were related to IBLD. Conclusions: Final data from the C-EDGE IBLD study indicate that EBR/GZR is well tolerated and effective in patients with HCV GT1 or 4 infection with IBLD. Disclosures Hézode: BMS: Consultancy; Janssen: Consultancy; MSD: Consultancy; AbbVie: Consultancy; Gilead: Consultancy. Fried:NIH: Research Funding; Gilead: Consultancy, Research Funding; TARGET PharmaSolutions: Equity Ownership; Merck: Consultancy, Research Funding; BMS: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding. Colombo:Merck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Tibotec: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Vertex: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lundbeck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GenSpera: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AlfaWasserman: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jennerex: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intercept: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bourlière:MSD: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Janssen: Consultancy; GSK: Consultancy; BMS: Consultancy. Ben-Ari:Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Strasser:MSD/Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Norgine: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Honoraria. Perumalswami:Merck: Research Funding; Gilead: Research Funding. Zamor:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lee:Eli Lilly: Consultancy; BMS: Research Funding; Gilead: Research Funding; Sanofi: Consultancy; Merck: Research Funding; Novartis: Consultancy. Satoskar:Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Research Funding. Sherman:AbbVie: Research Funding; Gilead: Research Funding; BMS: Research Funding; Merck: Consultancy, Research Funding. Morgan:Merck & Co., Inc.: Employment, Equity Ownership. Qiu:Merck: Employment. Hwang:Merck: Employment, Equity Ownership. Robertson:Merck: Employment, Equity Ownership. Nguyen:Merck: Employment. Barr:Merck: Employment, Equity Ownership. Wahl:Merck: Employment. Haber:Merck: Employment. Chase:Merck: Employment. Talwani:Merck & Co., Inc: Employment. Di Marco:Gilead: Research Funding.
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Nugroho, Sidiq Permono, and Syamsudin Syamsudin. "PENGUKURAN INDEKS KEPUASAN PENGGUNA DATA TERHADAP PELAYANAN PADA BADAN PUSAT STATISTIK KOTA SURAKARTA." Benefit: Jurnal Manajemen dan Bisnis 1, no. 1 (2016): 57. http://dx.doi.org/10.23917/benefit.v1i1.2366.
Full textAbstract:
This research aims was to figure out user’s satisfaction index towards this public service toward Central Bureau of Statistics (BPS). BPS is a non-ministry government institution implements the bureaucracy reform, and provides comprehensive, accurate, and sophisticated statistics in order to create a System of National Statistics. The data analysis technique for this research is Users (people who once used The Central Bureau of Statistic Service) Satisfaction Index, counted through weighted average values of some service elements based on Number 63/KEP/M.PAN/7/2003. Among the 120 users of The Central Bureau of Statistics, this research shows that The Satisfaction Index reaches 75.31 (good), but it still need to be improved remember there are some indicators showing a not quite good Performance Index. Totally 20 out of 24 indicators are categorized into ‘good service’, while the other fours indicator need to be enhanced and improved.
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Shah, Gaurav, Fady M. Mikhail, Harry P. Erba, and Nikolaos Papadantonakis. "Omission of Maintenance in Patients with High-Risk Acute Promyelocytic Leukemia (APL) in the Era of ATRA/Arsenic Consolidation." Blood 132, Supplement 1 (2018): 5192. http://dx.doi.org/10.1182/blood-2018-99-114872.
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Abstract Introduction: The role of maintenance treatment in patients with high-risk Acute Promyelocytic Leukemia (APL) in the era of ATO/ATRA is unclear. Methods: We retrospectively reviewed electronic medical records of patients with high-risk Acute Promyelocytic Leukemia (APL) and identified patients who did not receive maintenance. Results: We have identified 9 patients with high-risk APL who did not receive maintenance therapy. Five patients were females and 8 were white. The median age was 47-year-old (range 26-77 year old). The median WBC was 41,500 (range 14,700-167,500). The median blast percentage was 81% (range 1%-91%). The median platelet count was 28,000 (range 7,000-60,000). One patient received G-CSF prior to diagnosis of APL but the majority of cells on presentation were blasts. Two patients had additional cytogenetics changes apart from presence of t(15;17)(q22;21). Three patients had FLT3 ITD detected. All patients received ATRA during induction. Moreover, during induction 8 patients received Arsenic and all but one received Idarubicin. Seven of the 8 received Idarubicin according to Australasian APLM4 study. Bone marrow biopsies following induction were negative for PML/RARA by FISH analysis. RT-PCR for PML/ RARA was obtained at the time of the bone marrow (BM) biopsy in 8 patients and was negative. One patient had assessment close to the time of BM biopsy from peripheral blood and was negative. The median time from diagnosis to post Induction bone marrow was 49 days (range 32-56 days). All patients received 4 cycle of consolidation with ATRA and ATO according to Italian-German APL 0406 trial ( Lo-Coco et al., NEJM 2013). Three patients received Intrathecal chemotherapy for prophylaxis. Six of 9 had end-of-treatment bone marrow, which were negative for relapse. All patients were subsequently followed by RT-PCR for PML/RARA for molecular relapse. At last follow-up, all patients are alive and were in molecular remission. The median follow-up from diagnosis was 916 day (range 429-1674). Conclusion: We report our experience of high-risk APL patients in our institution who did not receive maintenance. None of the patients relapsed and our data suggest that patients that do not undergo maintenance in the era of ATO/Arsenic consolidation may remain in remission. Table. Table. Disclosures Erba: Takeda/Millenium: Research Funding; Pfizer: Consultancy, Other: grant; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Pfizer: Consultancy, Other: grant; Incyte: Consultancy, Speakers Bureau; Amgen: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas: Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Astellas: Research Funding; Seattle Genetics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Astellas: Research Funding; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Novartis: Consultancy, Speakers Bureau; Amgen: Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Astellas: Research Funding; Seattle Genetics: Consultancy, Research Funding; Janssen: Research Funding; Janssen: Research Funding; MacroGenics: Consultancy; MacroGenics: Consultancy; Pfizer: Consultancy, Other: grant; Juno: Research Funding; Juno: Research Funding; Pfizer: Consultancy, Other: grant; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Celgene: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; MacroGenics: Consultancy; Celgene: Consultancy, Speakers Bureau; Juno: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Juno: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Immunogen: Consultancy, Research Funding; Jazz: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding. Papadantonakis:Agios pharmaceuticals: Honoraria, Other: advisory board.
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Tsakiris, Dimitrios A., Johannes Oldenburg, Robert Klamroth, et al. "Effectiveness and Safety Outcomes in Patients with Hemophilia a Receiving Antihemophilic Factor (Recombinant) for at Least 5 Years in a Real-World Setting: 6-Year Interim Analysis of the Ahead International and German Studies." Blood 136, Supplement 1 (2020): 1. http://dx.doi.org/10.1182/blood-2020-139873.
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Introduction: Long-term effectiveness and safety data in patients treated in routine clinical practice settings can be captured from real-world studies. The international (INT) and German (GER) Antihemophilic factor (recombinant; rAHF) Hemophilia A (HA) outcome Database (AHEAD) studies assess long-term effectiveness and safety outcomes in patients with moderate HA (factor VIII level 1-5%) or severe HA (factor VIII &lt;1%) receiving rAHF (ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) in routine clinical practice. Methods: These are non-interventional, prospective, long-term, multicenter studies (INT: NCT02078427; GER: DRKS 00000556). Key outcomes include Gilbert scores (primary endpoint; pain scored 0-3; bleeding scored 0-3, and physical exam scored 0-12), annualized bleeding rates (ABRs) by disease severity, and adverse events (AEs). Findings reported here are from the 6-year interim analysis (data cut-off: July 15, 2019), and focus on patients who have received rAHF prophylaxis or on-demand (OD) treatment for ≥5 years in the studies. All data are reported for the safety analysis set (SAS), which comprised patients who passed screening and were assigned to a treatment group or regimen in the INT study, or were enrolled and have received ≥1 dose of rAHF since study enrollment in the GER study. Results: At the time of analysis, the INT study SAS comprised 707 patients, 156 of whom had received ≥5 years of rAHF treatment during the study. The GER study SAS comprised 382 patients, 231 of whom had received ≥5 years of rAHF treatment. Average Gilbert scores (all joints) were consistently low (years 1-6: median 0-1.0; mean 0-1.3) for both children aged 2 to &lt;12 years and adolescents aged 12 to &lt;18 years receiving rAHF prophylaxis within both studies. In the INT study, average Gilbert scores were lower with prophylaxis than with OD therapy in adults (aged ≥18 years) throughout the observation period (years 1-6: median: 0.9-1.4 [n=8-25] vs 1.4-6.3 [n=2-8], respectively; mean: 1.4-2.2 vs 2.1-6.3; respectively); significant differences (P&lt;0.05) between mean values were observed for years 3, 4, and 6. In the GER study, average Gilbert scores were slightly higher with prophylaxis than with OD in adults (years 1-6: median: 0.7-2.2 [n=12-37] vs 0.3-1.4 [n=2-15], respectively; mean: 1.0-2.7 vs 0.5-2.2, respectively; P-values not available). In the INT study, ABRs were consistently lower in patients receiving rAHF prophylaxis than in those receiving rAHF OD, irrespective of disease severity (Table). A similar trend was observed in the GER study in patients with severe HA, whereas ABRs were similar for both treatment regimens in patients with moderate HA. In both studies, greater proportions of patients with moderate or severe HA receiving rAHF prophylaxis had 0 bleeds than those receiving rAHF OD (Table). In the INT study, 842 AEs were reported in 116/156 (74.4%) patients, including 2 treatment-related serious AEs in 2 (1.3%) patients. In the GER study, 1321 AEs were reported in 197/231 (85.3%) patients, including 29 treatment-related serious AEs in 14 (6.1%) patients. Conclusions: These findings in patients receiving rAHF for ≥5 years in a real-world setting corroborate previous data on the long-term efficacy and tolerability of rAHF in patients with moderate or severe HA. rAHF demonstrated effectiveness in maintaining joint health (as measured by Gilbert scores) in adult patients. Table Disclosures Tsakiris: Roche: Research Funding; Shire, a Takeda company: Research Funding; Sobi: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Octapharma: Research Funding. Oldenburg:Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Klamroth:Pfizer: Consultancy, Research Funding, Speakers Bureau; Biotest: Speakers Bureau; Grifols: Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau. Guillet:CSL Behring: Research Funding, Speakers Bureau; Octapharma: Research Funding; Bayer: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Speakers Bureau; Roche-Chugai: Consultancy, Speakers Bureau. Khair:Shire, a Takeda company: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Baxalta/Shire, Takeda companies: Research Funding. Huth-Kühne:Bayer: Consultancy; CSL Behring: Consultancy; Shire, a Takeda company: Consultancy; Sobi: Consultancy. Kurnik:Sobi: Consultancy, Research Funding; Biotest: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau. Regensburger:Takeda Pharma Vertrieb GmbH & Co. KG: Current Employment, Current equity holder in publicly-traded company. Botha:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Fernandez:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Tang:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Ozelo:Pfizer: Consultancy, Research Funding; Shire/Takeda: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Bioverativ/Sanofi: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau.
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Rueping, Maria J. G. T., Werner J. Heinz, Anupma J. Kindo, et al. "Forty-One Recent Cases of Invasive Zygomycosis From a Global Clinical Registry." Blood 114, no. 22 (2009): 4736. http://dx.doi.org/10.1182/blood.v114.22.4736.4736.
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Abstract Abstract 4736 Background Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response is limited. Methods Fungiscope” - A Global Rare Fungal Infection Registry is a university-based case registry that collects data of patients with rare IFD, using a web-based electronic case form at www.fungiscope.net. Results Fourty-one patients with invasive zygomycosis were registered. Five were pediatric (12.2%), 28 (68.3%) male. Median age was 49 years (range 2-88). Most common underlying conditions were malignancies (n=26; 63.4%), diabetes mellitus (n=7; 17%) and solid organ transplant (n=4; 9.8%). Diagnosis was made by culture in 28 patients (68.3%), by histology in 26 patients (63.4%). Main sites of infection were lungs (n=24; 58.5%), soft tissues (n=8; 19.5%), rhino-sinu-orbital (n=8; 19.5%), brain (n=6; 14.6%). Disseminated infection of >1 non-contiguous sites was seen in 4 patients (9.8%). A favorable response was observed in 23 patients (56.1%). Overall survival was 51.2%. At diagnosis, ten patients (24.4%) were under continuous antifungal prophylaxis with itraconazole (n=1; 2.4%) or posaconazole (n=3; 7.3%). Empiric treatment was administered to 17 patients (41.4%). Survival was significantly improved in patients receiving active (n=7; 17.1%), as opposed to inactive empiric treatment (p=0.036). Initial targeted treatment with activity against zygomycetes was administered to 34 patients (82.9%). Liposomal amphotericin B was associated with improved response (p=0.012), and survival rates (p=0.004). Additional surgical treatment was performed in 21 patients (51.2%) and was not associated with improved response or survival. Conclusion Invasive zygomycosis is associated with low response rates to surgical and antifungal therapy. There was a marked amount of breakthrough infections under antifungal prophylaxis, including posaconazole. Only few patients received empiric treatment with activity against zygomycetes. Initial treatment with a polyene was associated with improved survival rates. Disclosures: Rueping: Essex/Schering-Plough: Speakers Bureau. Heinz:Schering-Plough/Essex: Consultancy, Research Funding, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Pfizer: Speakers Bureau. Rickerts:Gilead: Research Funding; pfizer: Research Funding. Lass-Floerl:Gilead: Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; MSD: Consultancy, Speakers Bureau. Herbrecht:Pfizer: Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Schering-Plough/Essex: Consultancy, Speakers Bureau. Silling:MSD: Consultancy, Research Funding; Pfizer: Research Funding; Astellas: Research Funding; Janssen-Cilag: Research Funding; Schering-Plough/Essex: Research Funding. Ullmann:Basilea: Consultancy; Aicuris: Consultancy; Pfizer: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Schering-Plough/Essex: Consultancy, Speakers Bureau; Astellas: Consultancy, Speakers Bureau. Maertens:MSD: Consultancy, Research Funding; Pfizer: Research Funding; Astellas: Consultancy; Bio-Rad: Consultancy; Nektar: Consultancy; Schering-Plough/Essex: Consultancy; Zeneus/Cephalon: Consultancy; Viropharma: Consultancy. Maschmeyer:Pfizer: Consultancy, Research Funding, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Vehreschild:Schering-Plough/Essex: Speakers Bureau; MSD: Speakers Bureau. Cornely:German Federal Ministry of Research and Education: Support - BMBF Grant 01KN0706; Astellas: Consultancy, Research Funding, Speakers Bureau; Basilea: Consultancy, Research Funding; Bayer: Research Funding; Genzyme: Research Funding; Gilead: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding; Merck/MSD: Consultancy, Research Funding, Speakers Bureau; Optimer: Research Funding; Schering-Plough/Essex: Consultancy, Research Funding, Speakers Bureau; Vicuron: Research Funding; F2G: Consultancy; Mölnlycke: Consultancy; Nektar: Consultancy; Zeneus: Consultancy; SpePharm: Speakers Bureau; United Medical: Speakers Bureau.
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Pagell, Ruth A. "Market Research in the US - Part 3: data from the US Economic Census." Business Information Review 12, no. 2 (1995): 52–63. http://dx.doi.org/10.1177/026638219501200205.
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The US Bureau of the Census conducts the Economic Census and the Census of Population and Housing, which form the basis for much of the demographic data available in the US. This article examines the Economic Census. It explains how the Census is organized, highlights those reports that are relevant to marketing and describes how to access the data.
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Stanko, Laura M., Luciano J. Costa, Denise Peker, Harry P. Erba, and Nikolaos Papadantonakis. "The Impact of Cumulative Dose of Cytarabine Consolidation on Outcomes in Older Patients with Acute Myeloid Leukemia." Blood 132, Supplement 1 (2018): 2687. http://dx.doi.org/10.1182/blood-2018-99-117769.
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Abstract Introduction: The optimum number of cycles and dose of Cytarabine consolidation in older patients (age 60 and above) with AML in first remission remains unclear. Methods: We retrospectively reviewed electronic medical records of patients. We identified 81 patients that were diagnosed with AML ( at age 60 and above) and received induction chemotherapy followed by Cytarabine consolidation between 2008 and 2017. Results: We reviewed the outcomes of 81 patients and report overall survival (OS) and relapse free survival (RFS) for the 69 patients reaching a landmark of 120 days from diagnosis without relapse or death (to exclude patients who would not be amenable to extended consolidation). Median follow up was 19.4 months (range 4.2-105.7). The median age at diagnosis was 65 (range 60-77); 86% were White. The majority were men (66%) ; 60% received daunorubicin-based induction [dose range 45 mg - 90 mg/m2] and 19% received re-induction chemotherapy. The cytogenetics based on ELN 2017 criteria were 71% intermediate, 13% favorable,10% adverse and for 6% not available (N/A.) From the 69 patients 16 were documented to be FLT3 ITD positive and 17 NPM1 positive. Twenty out of 69 patients (29%) received allogeneic hematopoietic cell transplantation (alloHCT). From those transplanted 5 patients were transplanted at CR2, one patient with relapse disease and the rest at CR1. Thirty patients relapsed and 27 patients died. At time of last follow up or death 56% of patients were on CR1, 13% on CR2 while the rest had relapsed disease [up to 3 relapses]. The median number of Cytarabine consolidation cycles was 2 (range 1-4 cycles) with Cytarabine total dose per cycle ranging between 6 gr/m2-18 gr/m2. The median cumulative dose from all cycles of consolidation was 18 gr/m2. We considered a cumulative dose ≤18 gr/m2 to be "low intensity (LI)" and > 18 gr/m2 "high intensity (HI)". OS was superior for HI patients [(Median not reached vs. 20.3 months, P=0.04), Figure 1a]. However there was no difference in RFS between groups [ median 14.3 Vs 14.8 months, p=0.6, Figure 1b]. When data were censored at the time of alloHCT, the OS advantage for HI was no longer statistically significant (p=0.07). In multivariate analysis for OS HI consolidation, intermediate and favorable risk cytogenetics had a favorable impact. Black race was associated with inferior OS. Since HI was associated with improved OS but not RFS we hypothesized that HI had better post relapse survival. In fact, there was a trend towards better post relapse survival among HI patients (N=15) compared to LI patients (N=15) [( median 12.4 vs. 5.2 months, p=0.070), Figure 1c]. Conclusion: The intensity of Cytarabine consolidation for older AML patients in CR1 was associated with improved OS but not RFS. Although the selection of LI or HI by the treating physician did not affect risk of relapse, our data suggest that HI consolidation is likely a surrogate for factors that make patients more amenable to successful post relapse therapy. Figure 1. Figure 1. Disclosures Costa: Amgen: Honoraria, Research Funding; Abbvie: Research Funding; Janssen: Research Funding; Karyopharm: Research Funding; BMS: Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria. Erba:Janssen: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; MacroGenics: Consultancy; Seattle Genetics: Consultancy, Research Funding; Astellas: Research Funding; Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Juno: Research Funding; Immunogen: Consultancy, Research Funding; Takeda/Millenium: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Seattle Genetics: Consultancy, Research Funding; MacroGenics: Consultancy; MacroGenics: Consultancy; Celgene: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Astellas: Research Funding; Juno: Research Funding; Seattle Genetics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Takeda/Millenium: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Jazz: Consultancy, Speakers Bureau; Janssen: Research Funding; Jazz: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Pfizer: Consultancy, Other: grant; Novartis: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Seattle Genetics: Consultancy, Research Funding; Pfizer: Consultancy, Other: grant; Agios: Consultancy, Speakers Bureau; Amgen: Research Funding; Agios: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Amgen: Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: grant; Immunogen: Consultancy, Research Funding; Pfizer: Consultancy, Other: grant; Celgene: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; MacroGenics: Consultancy; Juno: Research Funding; Juno: Research Funding; Agios: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Daiichi Sankyo: Consultancy, Research Funding. Papadantonakis:Agios pharmaceuticals: Honoraria, Other: advisory board.
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Paschka, Peter, Hervé Dombret, Xavier Thomas, et al. "Ivosidenib Improves Overall Survival Relative to Standard Therapies in Relapsed or Refractory Mutant IDH1 AML: Results from Matched Comparisons to Historical Controls." Blood 136, Supplement 1 (2020): 18–19. http://dx.doi.org/10.1182/blood-2020-136957.
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Background: A European Marketing Authorization Application for ivosidenib (IVO) is currently under review for the indication of mutant isocitrate dehydrogenase 1 (mIDH1) R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) in adult patients (pts) who have received ≥ 2 prior regimens, including ≥ 1 standard intensive chemotherapy (IC) regimen, or are not candidates for IC and have received ≥ 1 prior non-intensive regimen. IVO is an oral, potent, targeted inhibitor of mIDH1 and was approved by the FDA for the treatment of mIDH1 R/R AML in 2018, and in newly diagnosed AML in adults ≥ 75 years of age or pts ineligible for IC in 2019, based on the results of the open-label AG120-C-001 (NCT02074839) study. Aims: To evaluate the comparative benefit of IVO within the proposed EU indication, matched pt analyses were conducted using data on mIDH1 R/R AML pts from the AML Study Group (AMLSG) registry (NCT01252485) and a real-world chart review study (RWD) from France, Germany, UK, and Spain. Methods: Individual pt data from Arm 1+ of the AG120-C-001 study (n = 159) was compared to a historical control (HC), combining individual pt data from the AMLSG registry (n = 127) and the RWD (n = 148). A medical review was conducted to identify Arm 1+ IVO pts in the AG120-C-001 study and HC pts who fell within the proposed EU indication. Treatment with IVO was compared with the most recent therapy received by HC pts. HC pts treated with IC as their most recent therapy were excluded, as IVO pts, based on the AG120-C-001 study's eligibility criteria, were not considered candidates for IC. Propensity score-based matching/weighting methods were used to adjust for imbalances in baseline prognostic factors between the 2 cohorts (optimal full matching and inverse probability of treatment weighting [IPTW]). A literature review and data availability led to the inclusion of 6 baseline prognostic factors for estimation of propensity scores (age, history of hematopoietic stem cell transplantation, number of prior regimens for AML, nature of AML, cytogenetic risk, and primary refractory status). Balance between populations was assessed pre- and post-match via comparison of (weighted) standardized differences (SDs) for each covariate. Time-to-event data were summarized via Kaplan-Meier (KM) estimators with 2-sided 95% confidence intervals (CI). Cox regression analysis, using the key prognostic factors as covariates, was applied to estimate hazard ratios (HR) of overall survival (OS), and the corresponding 95% CI was estimated using the sandwich estimator. Complete remission (CR) rates were also compared between IVO pts and RWD non-IC HC pts (AMLSG pts were excluded as the response data did not allow for identification of CRs distinct from other response types). Results: One hundred and nine IVO pts and 60 HC pts fell within the proposed EU indication. The IPTW-matched dataset was selected for analysis, as it more strongly minimized the absolute weighted SDs between cohorts as compared with optimal full matching, with all SDs &lt; 0.05. Median OS was 8.1 months (mo) (95% CI: 5.7, 9.8) with IVO compared with 2.9 mo (95% CI: 1.9, 4.5) in the HC pts. The HR for OS was 0.396 (95% CI: 0.279, 0.562), strongly in favor of IVO (p &lt; 0.0001). There was clear and early separation of the IVO and HC KM curves, reflecting the early and sustained benefit of IVO treatment in this setting (Fig). Six- and 12-mo survival rates in the IVO cohort were 57.7% (95% CI: 48.2, 67.2) and 35.0% (95% CI: 25.7, 44.3), respectively, representing improvements versus 6- and 12-mo survival rates in the HC cohort of 29.1% (95% CI: 17.4, 40.8) and 10.8% (95% CI: 2.7, 18.9), respectively. The IVO cohort also demonstrated higher rates of CR than the HC cohort, with an observed CR rate of 18.3% (95% CI: 11.6, 26.9), compared with 7.0% (95% CI: 1.5, 19.1). Conclusion: IVO monotherapy demonstrated prolonged OS and the potential to increase CR rates vs standard of care therapies in a HC population. Disclosures Paschka: Amgen: Other; AbbVie: Other: Travel, accommodation or expenses, Speakers Bureau; Astellas Pharma: Consultancy, Speakers Bureau; Celgene: Consultancy, Other: Travel, accommodations or expenses; Sunesis Pharmaceuticals: Consultancy; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Otsuka: Consultancy; Janssen Oncology: Other; Astex Pharmaceuticals: Consultancy; Agios Pharmaceuticals: Consultancy, Speakers Bureau; BerGenBio ASA: Research Funding. Dombret:Novartis: Consultancy; Cellectis: Consultancy; Sunesis: Consultancy; Abbvie: Consultancy; Immunogen: Consultancy; Celgene: Honoraria; Amgen: Consultancy, Honoraria; Jazz Pharma: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Shire: Honoraria; Otsuka: Consultancy, Honoraria; Menarini: Honoraria; Daiichi Sankyo: Consultancy, Other: travel, accommodation expenses; Incyte: Consultancy, Other: travel, accommodation expenses; Celyad: Consultancy. Montesinos Fernandez:Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vyas:Astellas: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Forty Seven: Research Funding; Pfizer: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; AbbVie: Speakers Bureau. Kreuzer:Daiichi Sankyo: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Chugai: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Grifols: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Hexal: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Otsuka: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Ariad: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Baxalta: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Biotest: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau. Heuser:Karyopharm: Research Funding; Janssen: Consultancy; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Abbvie: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; BerGenBio ASA: Research Funding; Bayer: Consultancy, Research Funding; PriME Oncology: Honoraria. Metzeler:Daiichi Sankyo: Honoraria; Otsuka Pharma: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy; Astellas: Honoraria. Quesnel:Abbvie: Other: travel expenses; Daichii Sankyo: Other: travel expenses, Research Funding. Mohty:Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. De Botton:Pierre Fabre: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Servier: Consultancy; Celgene: Consultancy, Honoraria, Speakers Bureau; Agios: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Syros: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Seattle Genetics: Honoraria; Janssen: Consultancy, Honoraria. Döhner:Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Consultancy; Astellas Pharma: Consultancy; Astex Pharmaceuticals: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Sunesis Pharmaceuticals: Research Funding; Janssen: Consultancy, Honoraria; Agios: Consultancy; Novartis: Honoraria, Research Funding; Abbvie: Consultancy. Milkovich:RJM Group LLC: Current Employment. Reitan:RJM Group LLC: Current Employment. MacDonald:IQVIA: Current Employment. Casso:IQVIA: Current Employment. Storm:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Liu:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Kapsalis:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Attar:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Winkler:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Döhner:Agios: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Astex: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Oxford Biomedicals: Consultancy, Honoraria; Helsinn: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Sunesis: Other, Research Funding.
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Palla, Roberta, Marzia Menegatti, Marco Boscarino, et al. "Prospective Evaluation of Bleeding Incidence in Fibrinogen Deficiency (PRO-RBDD Study)." Blood 128, no. 22 (2016): 207. http://dx.doi.org/10.1182/blood.v128.22.207.207.
Full textAbstract:
Abstract BACKGROUND: Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenaemia) or both (hypodysfibrinogenaemia) of fibrinogen. Afibrinogenemia is associated with mild-to-severe bleeding, whereas hypofibrinogenemia is most often asymptomatic. Previously, our group (Peyvandi et al, JTH 2006) showed that in a group of 100 patients with afibrinogenemia and hypofibrinogenemia, the mean annual incidence of bleeding episodes was 0.7 on on-demand therapy (range 0-16.5) and 0.5 on prophylactic replacement therapy (range 0-2.6). Dys- and hypodysfibrinogenemia are commonly associated with bleeding, thrombosis, or both; however, most individuals are asymptomatic. Treatment of fibrinogen deficiency is challenging because the minimum amount of fibrinogen to prevent bleeding is unknown and because thromboembolism may occur in association with fibrinogen substitution therapy. Therefore a guideline for optimal treatment is not available yet. AIMS: The 3-year observational prospective study on rare bleeding disorders (PRO-RBDD) aimed at evaluating the incidence of bleeding episodes in patients with fibrinogen deficiency and the benefits and complication of current treatment regimens. METHODS: 17 Hemophilia Treatment Centers worldwide collected data in a web-based database at baseline (patient history) and at pre-specified time-points (every 6 months, follow up study); 146 patients (86 females/60 males) were recorded. Analysis was carried out on patients with available data on both antigen and activity levels. Bleeding incidence was calculated to evaluate number of bleeding episodes in patients on on-demand therapy. A survival analysis was also made to evaluate the cumulative incidence of the first bleeding requiring replacement therapy. Analysis was done using R v.3.3.1 (R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Data on activity and antigen level were available on 96 patients (54 females/42 males), of whom 81 are currently on follow up. Twenty-one (26%) patients were afibrinogenemic, 17 (21%) hypofibrinogenemic, 36 (44%) dysfibrinogenemic and 7 hypodysfibrinogenemic (9%), according to standard classification. Patients were followed up for a median of 810 days (IQR: 728-916, min-max: 221-1215). In on-demand therapy, the bleeding incidence was 0.86 patient-year-1 (95%CI 0.57-1.15) in afibrinogenemia, 0.30 (95%CI 0.15-0.52) in hypofibrinogenemia, 0.14 (95%CI 0.06-0.25) in dysfibrinogenemia and 0.06 (95%CI 0.-0.27) in hypodysfibrinogenemia. At 1200 days of follow up, the bleeding cumulative incidence of the first bleeding treated with replacement therapy was 0.43 (95%CI 0.11-0.64) in afibrinogenemia, 0.30 (95%CI 0.05-0.49) in hypofibrinogenemia, 0.06 (95%CI 0.0-0.14) in dysfibrinogenemia and 0.14 (95%CI 0.0-0.37) in hypodysfibrinogenemia. Prophylaxis regimen (dosage range 50 - 666 mg/Kg/month) with fibrinogen concentrate was used only in one third of patients (6/21) with afibrinogenemia and it seems to reduce the median number of bleeding events per year [from 1 (min-max: 1-3/year) to 0.4 (min-max: 0-1.25)]. Only one allergic reaction and no thrombotic events were reported. CONCLUSION: The results of this prospective observational study on patients with fibrinogen deficiency showed that the bleeding incidence decreased accordingly to plasmatic fibrinogen levels. Preliminary data on a limited number of patients with afibrinogenemia showed a reduction of bleeding episodes even if a wide range of prophylaxis dosage has been used. A larger group of patients and a longer follow up period are required to evaluate the efficacy of prophylaxis and to find the optimal target level to prevent spontaneous major bleeding in afibrinogenemic patients. Disclosures Palla: Pfizer: Other: travel support . Menegatti:Pfizer: Other: travel support . Blatny:CSL Behring: Speakers Bureau. Halimeh:Bayer Healthcare GmbH: Research Funding, Speakers Bureau; Baxalta Innovations GmbH: Research Funding, Speakers Bureau; Biotest AG: Research Funding, Speakers Bureau; CSL Behring GmbH: Research Funding, Speakers Bureau; Novartis Pharma GmbH: Speakers Bureau; Novo Nordisk Pharma GmbH: Research Funding, Speakers Bureau; Octapharma GmbH: Research Funding, Speakers Bureau; LFB GmbH: Speakers Bureau; Pfizer Pharma GmbH: Research Funding, Speakers Bureau. Siboni:LFB: Speakers Bureau; Bayer: Speakers Bureau. Laros-Van Gorkom:Baxter: Research Funding; CSL Behring: Research Funding; Sanquin: Speakers Bureau. Schutgens:CSL Behring: Research Funding; Pfizer: Research Funding; Bayer: Research Funding; Baxalta: Research Funding; Novonordisk: Research Funding. De Moerloose:Bayer: Consultancy, Research Funding, Speakers Bureau; Baxalta: Consultancy, Research Funding, Speakers Bureau; LFB: Speakers Bureau; Stago: Speakers Bureau; Novonordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy, Research Funding; Instrumentation Laboratory: Consultancy, Research Funding. Casini:CSL Berhing: Speakers Bureau; Bayer: Other: Travel support. Makris:CSL Behring: Consultancy; Novo Nordisk: Consultancy; Freeline Therapeutics: Consultancy; Bayer: Speakers Bureau; Biogen: Speakers Bureau; Grifols: Speakers Bureau. Chapin:Baxalta: Consultancy; CSL Behring: Consultancy; Novo Nordirsk: Consultancy; Alexion Pharmaceuticals: Consultancy; Apopharma: Consultancy; Bayer: Consultancy. Peyvandi:CSL Behring: Speakers Bureau; Novo Nordisk: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; Ablynx: Membership on an entity's Board of Directors or advisory committees, Other: research funding paid to Luigi Villa Foundation, Research Funding; Grifols: Speakers Bureau; SOBI: Speakers Bureau; Kedrion Biopharma: Consultancy, Other: research funding paid to Luigi Villa Foundation, Research Funding; LFB: Consultancy; Alexion: Other: research funding paid to Luigi Villa Foundation, Research Funding; Octapharma: Consultancy; Bayer: Speakers Bureau; Biotest: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau.
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Kreuter, M., F. Bonella, G. Riemekasten, et al. "AB0584 DOES ANTI-ACID TREATMENT INFLUENCE DISEASE PROGRESSION IN SYSTEMIC SCLEROSIS INTERSTITIAL LUNG DISEASE (SSC-ILD)? DATA FROM THE GERMAN SSC-NETWORK." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1589. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3069.
Full textAbstract:
Background:Gastroesophageal reflux (GER) is common in SSc and thus treatment with anti-acid therapy (AAT) is frequent. An association between GER and the development / progression of SSc-ILD has been hypothesized. However, outcomes of AAT on disease progression in SSc-ILD has only sparsely been studied.Objectives:Methods:The German Network for Systemic Scleroderma (DNSS), which includes SSc pts. prospectively, was analyzed for SSc-ILD. Those without progression at ILD 1stdiagnosis were categorized in AAT vs. no-AAT users and disease outcome was assessed.Results:SSc-ILD was reported in 1165 (28.2%) out of 4131 pts. 712 of SSc-ILD pts had no disease progression at ILD 1stdiagnosis. 567 used AAT while 145 did not. Baseline characteristics were similar between groups with regards to age (mean 54.7 years), BMI, time since SSc diagnosis and immunosuppressant use. Significant differences in no-AAT vs. AAT were found for gender (male 18% vs. 25%, p=0.05), SSc subtype (p=0.002, diffuse more common in AAT), lung function (DLCO 66% vs. 58%, p=0.001; FVC 86% vs. 77%, p=0.001), mRSS (8 vs. 11.5, p<0.01), esophageal involvement (32% vs. 56%, p<0.01) and steroid use (30% vs. 43%, p=0.005). While mortality did not differ between groups (3.9%, p= 0.59), disease progression was more common in the AAT group than in no-AAT users (24.5% vs. 13%, p=0.03). Furthermore, there was a significant difference in decline of FVC≥10% with 30% in the AAT compared to 14% in no-AAT (p=0.018); a decline in DLCO≥15% was more common in the AAT group by trend (23% vs. 14%, p=0.087).Conclusion:While results may have partially been biased by differences in baseline characteristics, this current analysis disfavors the approach of AAT use for SSc-ILD.Disclosure of Interests:Michael Kreuter Grant/research support from: Roche, Boehringer, Consultant of: Roche, Boehringer, Speakers bureau: Boehringer, Roche, Francesco Bonella Grant/research support from: Boehringer, Consultant of: Boehringer, Roche, Bristol MS, Galapagos, Speakers bureau: Boehringer, Roche, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Ulf Müller-Ladner Speakers bureau: Biogen, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,, Elise Siegert Grant/research support from: Actelion, Consultant of: AEC, Speakers bureau: NA, Claudia Guenther: None declared, Ina Koetter Grant/research support from: Novartis, Roche, Speakers bureau: Abbvie, Actelion, Celgene, MSD, UCB, Sanofi, Lilly, Pfizer, Novartis, Chugai, Roche, Boehringer, Norbert Blank Speakers bureau: Actelion, Roche, Boehringer, Pfizer, Chugai, Christiane Pfeiffer: None declared, Marc Schmalzing: None declared, Gabriele Zeidler: None declared, PETER KORSTEN Grant/research support from: Novartis, Juarms GmbH, Consultant of: Abbvie, Pfizer, Lilly, BMS, Speakers bureau: Abbvie, Pfizer, chugai, BMS, Lilly, Sanofi aventis, Laura Susok: None declared, Aaron Juche: None declared, Margitta Worm Consultant of: Mylan Gemany, Bencard Allergie, BBV Technologies S.A., Novartis, Biotest, Sanofi, Aimmune Therapies, Regeneron, Speakers bureau: ALK-Abello, Novartis, Sanofi, Biotest, Mylan, Actelion, HAL Allergie, Aimmune Bencard Allergie, Ilona Jandova: None declared, Jan Ehrchen: None declared, Cord Sunderkoetter: None declared, Gernot Keyszer: None declared, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Tim Schmeiser Speakers bureau: Actelion, UCB, Pfizer, Alexander Kreuter Speakers bureau: Sanofi, Abbvie, Merck Sharp&Dohme, Boehringer, Kathrin Kuhr: None declared, Hanns-Martin Lorenz Grant/research support from: Consultancy and/or speaker fees and/or travel reimbursements: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly. Scientific support and/or educational seminars and/or clinical studies: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, Thermo Fisher., Consultant of: see above, Pia Moinzadeh: None declared, Nicolas Hunzelmann Speakers bureau: Actelion, Boehringer
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Pipe, Steven W., Michael Recht, Nigel S. Key, et al. "First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies." Blood 136, Supplement_2 (2020): LBA—6—LBA—6. http://dx.doi.org/10.1182/blood-2020-143560.
Full textAbstract:
Background: Etranacogene dezaparvovec is an investigational gene therapy for hemophilia B (HB) comprising an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with a liver specific promoter. In a Phase 2b study, a single dose of etranacogene dezaparvovec provided mean FIX activity of 41.0% sustained at 1yr post-dose in 3 participants (pts). Although most gene therapy clinical studies exclude pts with pre-existing neutralizing antibodies (NAbs) to the capsid serotype, early clinical studies and nonhuman primate data suggest that generally prevalent titers of anti-AAV5 NAbs may not preclude successful transduction with etranacogene dezaparvovec. Aims: A Phase 3, Health Outcomes with Padua gene; Evaluation in Hemophilia B (HOPE-B; NCT03569891) was established to further assess efficacy and safety of etranacogene dezaparvovec in adults with HB with a wide range of pre-existing NAbs to AAV5. Here we report outcomes at 26 weeks (wks). Methods: HOPE-B is a Phase 3, open-label, single-dose, single-arm, multi-national trial in adult males with severe or moderate-severe HB (FIX≤2%). All pts received routine FIX prophylaxis prior to study. Pts were not excluded based on pre-existing NAbs to AAV5. Pts entered a prospective lead-in period of at least 6 months during which bleeding/factor use was monitored, then received a single intravenous dose of etranacogene dezaparvovec (2x1013 gc/kg). Pts will be followed for 5yrs. Primary endpoints comprised FIX activity (one stage) at 26 and 52wks after dosing and 52wk annualized bleeding rate. For pts with no clean post-treatment FIX samples (≥10d post exogenous FIX), factor activity was imputed as baseline value based on historic disease severity. Secondary endpoints include factor replacement use, adverse events (AEs), and reactive use of corticosteroids. Results: 75 pts were screened, of whom 67 entered lead-in. 54 pts were dosed (44 severe, 10 moderately severe HB) and completed 26wks of follow-up. Mean age (±SD) was 41.5 (15.8) yrs. 38/54 pts (70.4%) had bleeds (n=123) during the lead-in despite prophylaxis, and 23/54 (42.6%) had NAbs to AAV5 at baseline (max titer: 3212.3). Following treatment, FIX activity increased rapidly to a mean (SD; min,max) of 37.2% (±19.6; 1.0, 97.1) at wk26, representing a mean (SD; min,max) change from baseline of 36.0% (±19.7; 0, 96.1 p&lt;0.0001, confirmed by per-protocol sensitivity analysis). No correlation of pre-existing NAbs with FIX activity was identified up to a titer of 678.2; n=52, R2 = 0.078); a single pt had a NAb titer of 3212.3 and did not respond. In addition to this pt, one other pt received a partial dose and remained on prophylaxis; all other pts (96.3%) successfully discontinued routine prophylaxis. 39/54 (72.2%) pts reported 0 bleeds in the first 26wks post-treatment; 15 pts reported a total of 21 bleeds. Mean (SD) annualized FIX consumption (IU/yr/pt) was 292,304 (±171,079) during lead-in, decreasing to 12,622 (±36,466) at wk26 (96.0% reduction, N=54). Overall, 37/54 (68.5%) pts had any treatment-related AE post-treatment, the majority of which were mild (81.5%). No deaths occurred and no treatment-related SAEs were reported. 7 pts had infusion-related reactions; the infusion was discontinued in 1 pt. Treatment-related elevations in liver enzymes were reported in 9 pts and received steroids per protocol. All discontinued steroid use prior to wk26 and FIX activity was preserved in the mild range. In addition to these, the most frequent treatment-related AEs were headache (13.0%) and influenza-like illness (13.0%). No inhibitors to FIX were reported. No relationship between safety and NAbs was observed. Conclusions: The first co-primary endpoint of this study was met. This is the first report of a Phase 3 study in HB and the largest gene therapy trial cohort to date. Following a single dose of etranacogene dezaparvovec, FIX activity increased, without the need for prophylactic immunosuppression, into the mild-to-normal range at 26wks in pts with severe/moderately severe HB. Importantly, this included pts with titers of pre-existing anti-AAV5 NAbs. Pts were able to discontinue prophylaxis and bleeding was abolished in the majority. The safety profile was consistent with early phase AAV5 studies and together these data support a favorable safety and efficacy profile for etranacogene dezaparvovec Disclosures Pipe: HEMA Biologics: Consultancy, Other; Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; ApcinteX: Consultancy; Bayer: Consultancy, Other: Contracted Research; BioMarin: Consultancy, Other: Contracted Research; Takeda: Consultancy; uniQure: Consultancy, Other; Siemens: Other; Pfizer: Consultancy; Freeline Therapeutics: Consultancy, Other: Contracted Research; Novo Nordisk: Consultancy, Other: Contracted Research; Roche/Genentech: Consultancy, Other: Contracted Research; Sangamo Therapeutics: Consultancy; Sanofi Genzyme: Consultancy, Other; Spark Therapeutics: Consultancy. Recht:CSL Behring: Consultancy, Other: personal fees; Genentech: Consultancy, Other: personal fees, Research Funding; Pfizer: Consultancy, Other: personal fees, Research Funding; BioMarin: Research Funding; Takeda: Consultancy, Other: personal fees, Research Funding; uniQure: Consultancy, Other: personal fees, Research Funding; Novo Nordisk: Consultancy, Other: personal fees, Research Funding; Spark: Research Funding; Bayer: Research Funding; Grifols: Research Funding; Hema Biologics: Consultancy, Research Funding; LFB: Research Funding; Octapharma: Research Funding; Catalyst Biosciences: Consultancy; Kedrion: Consultancy; Sanofi: Consultancy, Research Funding. Key:Uniqure: Consultancy; Grifols: Research Funding; Takeda: Research Funding; Novo Nordisk: Other: Chair of Grants Committee. Leebeek:Shire/Takeda: Research Funding; uniQure: Consultancy; Shire/Takeda: Consultancy; BioMarin: Consultancy; SOBI: Other: Travel grant; Roche: Other: DSMB member for a study; CSL Behring: Research Funding. Castaman:Bayer, Roche, Sobi, Grifols, Novo Nordick, Werfen, Kedrion: Consultancy, Honoraria, Speakers Bureau; CSL Behring, Pfizer, Sobi: Research Funding; Ablynx, Alexion, Bayer, Takeda, CSL Behring, Novo Nordisk, Pfizer, Roche,Sanofi, SOBI, uniQure: Membership on an entity's Board of Directors or advisory committees. Lattimore:uniQure: Other: Study Steering Committee member. Van Der Valk:Baxalta: Research Funding. Peerlinck:Bayer: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Roche: Research Funding; Sobi: Consultancy; Takeda: Consultancy, Research Funding. Coppens:Roche: Research Funding; Portola/Alexion: Research Funding; Sanquin Blood Supply: Research Funding; uniQure: Research Funding; NovoNordisk: Consultancy; Pfizer: Consultancy; Sobi: Consultancy; Medcon International: Consultancy; MEDtalks: Consultancy; Bayer: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; Daiichi Sankyo: Research Funding. O'Connell:uniQure: Consultancy; F. Hoffmann-La Roche Ltd, Novo Nordisk, SOBI: Speakers Bureau; SOBI: Research Funding. Pasi:Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; uniQure: Other: Grants and nonfinancial support , Research Funding; ApcinteX: Consultancy, Other: Personal fees ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Roche: Honoraria, Other; Sobi: Consultancy, Honoraria, Other; Tremeau: Consultancy. Kampmann:Uniqure: Research Funding, Speakers Bureau; Shire Pharmaceuticals: Speakers Bureau. Meijer:Pfizer: Research Funding; Sanquin: Speakers Bureau; Bayer: Speakers Bureau; Sanquin: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Speakers Bureau; BMS: Speakers Bureau; Aspen: Speakers Bureau; Uniqure: Consultancy. von Drygalski:Biomarin: Consultancy; Bioverativ/Sanofi Genzyme: Consultancy; NovoNordisk: Consultancy; Pfizer: Consultancy; uniQure: Consultancy; Hematherix Inc.: Membership on an entity's Board of Directors or advisory committees. Young:Genentech/Roche, Grifols, and Takeda: Research Funding; BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy. Hermans:WFH: Other; EAHAD: Other; LFB: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau. Astermark:Bayer, CSL Behring, Novo Nordisk, Octapharma, Roche, Sobi, Spark, Takeda, uniQure: Consultancy; uniQure: Research Funding. Klamroth:Bayer: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche/Chugai: Consultancy, Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Biotest: Speakers Bureau; LEO: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lemons:uniQure: Research Funding. Visweshwar:Biogen Idec: Membership on an entity's Board of Directors or advisory committees. Escobar:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Biomarin, Genetech/Roche, CSL Behring, Kedrion, Magellan Healthcare: Honoraria. Gomez:Global Blood Therapeutics: Speakers Bureau. Kruse-Jarres:CSL Behring, Genentech, Inc., Spark: Research Funding; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Honoraria; F. Hoffmann-La Roche Ltd: Speakers Bureau; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Consultancy. Kotowski:uniQure: Research Funding. Quon:Orthopaedic Institute for Children: Current Employment; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Octapharma: Honoraria; Shire/Takeda: Speakers Bureau. Wang:Bayer: Honoraria; Takeda: Honoraria; Genentech: Honoraria; Biomarin: Honoraria; CSL Behring: Honoraria; Bioverativ Inc: Honoraria; Catalyst Biologics: Consultancy; NovoNordisk: Consultancy; Hema biologics / LFB: Consultancy. Wheeler:Takeda: Membership on an entity's Board of Directors or advisory committees; uniQure: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Sawyer:uniQure: Current Employment, Current equity holder in publicly-traded company. Verweij:uniQure: Current Employment. Colletta:uniQure: Current Employment. Bajma:uniQure: Current Employment. Gut:uniQure: Current Employment. Miesbach:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Freeline: Consultancy, Membership on an entity's Board of Directors or advisory committees; LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; uniQure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Etranacogene dezaparvovec is an investigational gene therapy
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Oldenburg, Johannes, María Teresa Alvarez Román, Giancarlo Castaman, et al. "Real-World Effectiveness and Safety of BAY 94-9027 (Damoctocog Alfa Pegol) in Previously Treated Patients with Hemophilia A (HEM-POWR): Online Patient Portal and LIFE-ACTIVE Sub-Study." Blood 134, Supplement_1 (2019): 4943. http://dx.doi.org/10.1182/blood-2019-128140.
Full textAbstract:
Background and Rationale: BAY 94-9027 (damoctocog alfa pegol) is a site-specifically PEGylated B-domain deleted recombinant factor VIII (FVIII) with an extended half-life, approved for prophylaxis or treatment of bleeds in previously treated patients (PTPs) aged ≥12 with hemophilia A. The efficacy and safety of BAY 94-9027 was demonstrated in two phase II/III clinical studies in PTPs with severe hemophilia A, however, real-world data are still being gathered. The aim of the HEM-POWR study is to assess the effectiveness and long-term safety of BAY 94-9027 in the real-world clinical setting. Patients will be introduced to an online patient portal that provides study information as well as access to eDiaries and electronic patient-reported outcomes (ePROs) to patients to facilitate retention over the duration of the study. Patients will also be given the opportunity to participate in LIFE-ACTIVE, a sub-study analyzing the relationship between the patients' regular daily activity and the efficacy parameters collected during HEM-POWR. Here we present the features of the patient portal and describe the LIFE-ACTIVE sub-study design. Study Design and Methods: HEM-POWR (NCT03932201) is a multinational, multicenter, non-interventional, open-label, prospective, phase IV, cohort study. It aims to enroll ≥200 PTPs with hemophilia A receiving BAY 94-9027 (on-demand, prophylaxis, or intermittent prophylaxis [as per local label]). Key exclusion criteria are presence or history of FVIII inhibitor (≥0.6 Bethesda units), diagnosis of any bleeding or coagulation disorder other than hemophilia A, or treatment with immune tolerance induction at enrollment. The primary objective of HEM-POWR is to assess the effectiveness of prophylaxis with BAY 94-9027 in the real-world setting through the collection of total bleeding events and analysis of annualized bleeding rate. Secondary objectives include long-term safety, joint health, location and number of target joints, hemostasis during surgery and PROs. Patient enrollment, adherence and retention can be difficult in observational hemophilia studies. The patient portal for this study aims to overcome these challenges by providing study- and product-related information. It also aims to lessen the burden for patients in the study by providing e-solutions to collect their study data, including the ability to complete the study diary, and PRO measures online. The portal also includes videos explaining the study and study procedures, and is country-customized with links to relevant websites. Patients participating in LIFE-ACTIVE will be asked to wear an ActiGraph CP Insight activity-tracking smart watch continually for four 30-day periods, at their initial visit and then at months 12, 24 and 36. Measurements recorded will include physical activity intensity and duration, general mobility, and sleep quality and duration. All data will be transferred to a secure, cloud-based system and patients will not be aware of the values measured by the device. Participating countries include, but may not be limited to Austria, Belgium/Luxemburg, Canada, Colombia, Finland, Germany, Greece, Italy, Japan, Netherlands, Portugal, Saudi Arabia, Denmark, Norway, Sweden, Slovenia, Spain, Switzerland, Taiwan, and USA. The study will run from 2019 until 2025, with an observation period of ≥60 months. Disclosures Oldenburg: Octapharma: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Takeda (Shire): Consultancy, Research Funding, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; Swedish Orphan Biovitrum: Consultancy, Speakers Bureau. Alvarez Román:CSL Behring: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Sobi: Speakers Bureau; Bayer: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Speakers Bureau; Shire (Takeda): Research Funding, Speakers Bureau. Castaman:Shire: Speakers Bureau; Uniqure Kedrion: Speakers Bureau; Pfizer: Research Funding; CSL Behring: Research Funding, Speakers Bureau; Bayer: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Sobi: Research Funding, Speakers Bureau. Janbain:Shire (Vonvendi): Speakers Bureau; Genentech: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Shire: Consultancy, Honoraria; HTRS-MRA (Bioverativ Sanofi): Research Funding. Matsushita:uniQure: Consultancy, Honoraria; CSL: Consultancy, Honoraria; Bioverative: Research Funding; Pfizer: Consultancy, Honoraria; KM biologists: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria. Meijer:Sanquin: Research Funding; Pfizer, Sanquin, Uniqure: Research Funding; Uniqure, BMS, Aspen, Boehringer Ingelheim, Sanquin, Bayer: Consultancy, Honoraria; Bayer: Research Funding. Sanabria:Bayer: Employment. Reding:Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Biomarin: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.
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Jamy, Omer, Charles Bodine, Rehan Sarmad, et al. "Outcomes of Acute Myeloid Leukemia Patients with Indeterminate Day 14 Bone Marrow Results Treated with and without Re-Induction Chemotherapy." Blood 132, Supplement 1 (2018): 2688. http://dx.doi.org/10.1182/blood-2018-99-114090.
Full textAbstract:
Abstract Introduction: The initial response to standard induction chemotherapy for acute myeloid leukemia (AML) is commonly assessed with day 14 bone marrow evaluation; patients with residual disease may receive re-induction chemotherapy. The benefit of re-induction chemotherapy in patients with indeterminate day 14 bone marrow results (defined in our study as ≤ 20% cellularity and 5-20% blasts) remains unclear. We report our experience of AML patients with indeterminate day 14 bone marrow treated with and without re-induction chemotherapy. Methods: A retrospective chart review was performed to evaluate adult patients with newly diagnosed AML treated with and without re-induction chemotherapy for indeterminate day 14 bone marrow results between January 2010 and April 2018 at our institution. All patients included in the analysis received induction chemotherapy with cytarabine and an anthracycline. Approval for the study was obtained from the Institutional Review Board. Results: We identified 50 patients with indeterminate day 14 bone marrow results (Table 1). Twenty five patients (50%) received re-induction therapy and 25 (50%) did not. Flow cytometry data on day 14 bone marrow samples were available for 15 patients (60%) who received re-induction and 18 (72%) who did not. All flow cytometry samples, when performed, were reported as persistent/residual disease. The median age at diagnosis was 56 years (range 19-70) in patients who received re-induction and 59 years (range 23-73) in those who did not. There were 12 patients (48%) with poor risk disease, both in the re-induction arm (10 abnormal karyotype, 2 normal karyotype with molecular abnormalities) as well as in the no re-induction arm (6 abnormal karyotype, 6 normal karyotype with molecular abnormalities). FLT3-ITD mutation was positive at diagnosis in 2 cases (8%) in the re-induction arm and in 8 cases (32%) not receiving re-induction. The most commonly used chemotherapy regimen in the re-induction arm was fludarabine, high dose cytarabine and granulocyte-colony stimulating factor (FLAG, 56%). Fifteen patients (60%) in the re-induction arm and 17 (68%) in the no re-induction arm received post-remission consolidation therapy. High-dose cytarabine was the preferred consolidation regimen (96%). The overall response rate [complete remission (CR) + CR with incomplete count recovery (CRi)] was similar in both arms (80% vs. 80%). There was no statistically significant difference in median overall survival (OS) and relapse free survival (RFS) between the re-induction and no re-induction arms (Figure 1). In univariate analysis, no statistically significant difference in OS was found for age at diagnosis (≥ 60 years vs. < 60 years; p=0.06), white blood cell count at diagnosis (≥ 50,000 vs. < 50,000; p=0.48), disease risk status (poor risk vs. favorable/intermediate risk; p=0.81) and performance of transplant (yes vs. no; p=0.13) in the entire population. Conclusion: Our study did not find a statistically significant difference in overall response rates, as well as for OS and RFS in AML patients with indeterminate day 14 bone marrow receiving re-induction or not. Our findings question the utility of immediate re-induction chemotherapy and raise the concern for over treatment in this patient population. Larger studies investigating similar outcomes are warranted to validate these clinical findings. Table 1. Table 1. Disclosures Costa: Celgene: Honoraria, Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding; Janssen: Research Funding; Karyopharm: Research Funding; Sanofi: Honoraria; BMS: Research Funding. Saad:Actinium: Consultancy. Papadantonakis:Agios pharmaceuticals: Honoraria, Other: advisory board. Erba:Janssen: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; MacroGenics: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Juno: Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Daiichi Sankyo: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Astellas: Research Funding; Takeda/Millenium: Research Funding; Janssen: Research Funding; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Juno: Research Funding; Amgen: Research Funding; Immunogen: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Pfizer: Consultancy, Other: grant; Astellas: Research Funding; Agios: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Immunogen: Consultancy, Research Funding; Juno: Research Funding; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Astellas: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Takeda/Millenium: Research Funding; Amgen: Research Funding; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Janssen: Research Funding; Jazz: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda/Millenium: Research Funding; Janssen: Research Funding; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Pfizer: Consultancy, Other: grant; Agios: Consultancy, Speakers Bureau; Juno: Research Funding; MacroGenics: Consultancy; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: grant; Celgene: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: grant; Jazz: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Astellas: Research Funding; Incyte: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau.
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D'Agostino, Mattia, Anders Waage, Juan-José Lahuerta, et al. "Validation and Improvement Opportunities of the Revised International Staging System for Multiple Myeloma: An Analysis on Mature Data from European Clinical Trials within the Harmony Big Data Platform." Blood 134, Supplement_1 (2019): 1773. http://dx.doi.org/10.1182/blood-2019-124321.
Full textAbstract:
Background. The outcome of multiple myeloma (MM) patients is heterogeneous. In 2015, analyzing 4445 newly diagnosed MM (NDMM) patients enrolled into 11 clinical trials after a median follow-up of 46 months, a risk stratification algorithm named Revised-ISS (R-ISS) was developed combining International Staging System (ISS), chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization and serum lactate dehydrogenase (LDH) (Palumbo et al., JCO 2015). Here we report a mature follow-up of 5584 patients enrolled in 14 clinical trials, providing an updated report on the R-ISS prognostic role and highlighting potential improvements. Methods. Data from different European cooperative groups were collected through the European Myeloma Network (EMN) and registered in a big data platform developed by HARMONY, which is a European public-private partnership focusing on hematologic malignancies with unmet medical needs and providing a legal-ethical framework for international data sharing and analysis. The primary end point of this analysis was overall survival (OS) according to R-ISS. All NDMM patients received immunomodulatory agents (IMiDs) or proteasome inhibitors (PIs) as part of their upfront treatment. Results. 5584 NDMM patients with a median age of 65 years were analyzed after a median follow-up of 74 months. 35% of evaluable patients had ISS I disease, 40% ISS II and 25% ISS III. LDH was ≤ the upper limit of normal (ULN) in 87% of evaluable patients, >ULN in 13%. To define high-risk CA, we performed a multivariate Cox model for OS individually evaluating del(17p), t(4;14) and t(14;16) positivity. Del(17p) (HR 1.78, p<0.001) and t(4;14) (HR 1.67, p<0.001) confirmed their role as independent risk factors, while t(14;16) (HR 1.19, p=0.16) did not. We therefore defined high-risk CA as del(17p) and/or t(4;14) positivity. High-risk CA were present in 23% of evaluable patients, while low-risk CA in 77%. Overall, 3674 patients (66%) had complete ISS, CA and LDH data and were thus eligible for R-ISS analysis. Baseline characteristics and OS of patients with complete vs incomplete data (median OS 80.6 vs 80.2 months, p=0.95) were similar, excluding a selection bias. R-ISS I was calculated as ISS I, no high-risk CA [del(17p) and/or t(4;14)] and normal LDH; R-ISS III was calculated as ISS III and high-risk CA or high LDH; R-ISS II included all the other possible combinations. 962 (26.2%) patients had R-ISS I disease, 2334 (63.5%) R-ISS II and 378 (10.3%) R-ISS III. Median OS was 158.6 months for R-ISS I, 71.1 months for R-ISS II and 36.6 months for R-ISS III patients (Figure 1). 5-year OS rates were 80%, 56% and 34%, while 10-year OS rates were 60%, 33% and 13% for R-ISS I, II and III respectively. In a multivariate Cox model, R-ISS II vs I (HR 2.20, 95% CI 1.94-2.5), R-ISS III vs I (HR 4.58, 95% CI 3.88-5.4), male sex (HR 1.20 vs female sex, 95% CI 1.09-1.31) and age >65 years (HR 1.62 vs ≤65 years, 95% CI 1.47-1.78) significantly increased the risk of death (p<0.001). The prognostic role of R-ISS was also confirmed in the 1244 patients that were not included in the original R-ISS report (R-ISS II vs I HR 2.38, R-ISS III vs I HR 4.40, p<0.001), validating it. The prognostic role of R-ISS was confirmed by subgroup analyses on: transplant-eligible patients [2161, 58.8%; both receiving (1611, 43.8%) or not receiving (550, 15.0%) transplant]; transplant-ineligible patients (1513, 41.2%); and patients receiving PIs (874, 23.8%), IMiDs (1669, 45.4%) or both (1131, 30.8%). We next tested whether additional factors can impact OS in a multivariate Cox model including R-ISS, age and sex. NDMM patients with an IgA monoclonal component showed a worse OS compared to non-IgA patients (HR 1.21, p<0.001). A baseline creatinine clearance ≤45 ml/min independently predicted OS, as compared to a normal renal function (HR 1.24, p<0.001). The amp(1q) effect on OS was solid (HR 1.45, p<0.001), although data were only available in 1231 patients due to many missing values. Patients with a poor prognostic performance status (ECOG >1 or Karnofsky <80) were at higher risk of death as well (HR 1.36, p<0.001). Conclusion. We confirmed the prognostic role of R-ISS within the largest cohort of NDMM patients analyzed so far. Moreover, we detected other independent OS predictors that can help us to further refine the current prognostic method. The addition of new datasets is planned; the improvement of the current R-ISS may foster a worldwide collaboration. Disclosures Lahuerta: Takeda, Amgen, Celgene and Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bertsch:Celgene: Other: travel support; Sanofi: Other: travel support. Zamagni:Celgene Corporation: Honoraria, Other: Advisory board, Speakers Bureau; Janssen: Honoraria, Other: Advisory board, Speakers Bureau; Amgen: Honoraria, Other: Advisory board, Speakers Bureau; BMS: Honoraria, Other: Advisory Board, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Sanofi: Honoraria, Other: Advisory Board, Speakers Bureau. Bullinger:Seattle Genetics: Honoraria; Janssen: Honoraria; Hexal: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Daiichi Sankyo: Honoraria; Bristol-Myers Squibb: Honoraria; Bayer: Other: Financing of scientific research; Astellas: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Menarini: Honoraria; Jazz Pharmaceuticals: Honoraria. Larocca:Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Mateos:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; EDO: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Van De Donk:Roche: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; AMGEN: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding. Salwender:Janssen Cilag: Consultancy, Honoraria, Other: Travel grants; Celgene: Honoraria, Other: Travel grants; AMGEN: Honoraria, Other: Travel grants; Sanofi: Honoraria, Other: Travel grants; Bristol-Myers Squibb: Honoraria, Other: Travel grants; Takeda: Honoraria, Other: Travel grants; Oncopeptides: Honoraria, Other: Travel Grants. Bladé:Jansen, Celgene, Takeda, Amgen and Oncopeptides: Honoraria. Tacchetti:Janssen: Honoraria; BMS: Honoraria; Oncopeptides: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Zweegman:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Goldschmidt:Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; MSD: Research Funding; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Molecular Partners: Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; ArtTempi: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Research Funding; John Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product. Cavo:bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Sonneveld:SkylineDx: Research Funding; Takeda: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria, Research Funding. Boccadoro:Sanofi: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Celgene: Honoraria, Research Funding. OffLabel Disclosure: This presentation includes discussion of off-label use of a drug or drugs for the treatment of multiple myeloma.
21
Abed, Baraa Uday, and Suha Ali Husaien. "Crises Management Analyses of Iraqi Swimming Federation’s Administrative Bureau." Journal of Physical Education 33, no. 1 (2021): 129–37. http://dx.doi.org/10.37359/jope.v33(1)2021.1122.
Full textAbstract:
The research aimed at identifying the reality of crises management in central administrative bureau in governorates swimming federation from the administrative bureaus’ point of view as well as first class referees. The problem of the research lies in answering whether the central or regional administrative bureaus of Iraqi swimming federation are able to administer crises that they face. The researchers used the descriptive method on 85 member and referee who represent Iraqi central swimming federation as well as regional federation. The subjects were (80) members and referees. A scale was designed for crises administrations that was applied on the subject. The data was collected and treated to come up with the conclusions. The researchers concluded that crises administration reality shows great weakness that leads to increasing the effects of these crises that negatively affected the federation.
22
Van den Berg, Marijke, Kathelijn Fischer, Elena Santagostino, et al. "99.3% of Inhibitors in Severe Hemophilia a Develop before Exposure Day 75. Time to Change Definition of Previously Treated Patients; Data from 1038 Patients with Severe Hemophilia a of the Pednet Registry." Blood 132, Supplement 1 (2018): 2472. http://dx.doi.org/10.1182/blood-2018-99-114518.
Full textAbstract:
Abstract Introduction.In patients with hemophilia treated with factor VIII products, the development of inhibitory antibodies poses the largest safety risk. Especially during the first 50 exposure days (EDs), up to 37% of patients with severe hemophilia A have been reported to develop an inhibitor. To study neo-immunogenicity of products and new treatment strategies, patients have been distinguished into previously untreated (PUPs) and previously treated patients (PTPs); the latter defined as patients treated for more than 150 EDs. The number of 150 EDs was established in the eighties during a time when most patients received on-demand treatment and testing for inhibitors was not frequently performed. More recent studies on inhibitor incidence in PUPs with severe hemophilia A report that 50% of inhibitors develop within 14-15 EDs, however the cut-off number of EDs for a PUP to become a PTP is not well defined. The aim of this study was to define the number of EDs for PUPs to become PTPs based on long-term follow-up of patients with severe hemophilia A Methods.All patients with severe hemophilia A born after January 1, 2000, treated for at least 1 ED and followed prospectively until inhibitor development or the number of EDs at last follow-up, were included. The number of EDs at inhibitor development is the last exposure day before the first positive titer was reported. An inhibitor was defined as positive when at least two positive inhibitor titers were measured. Positivity was defined according to the cut-off level in each individual center's laboratory. Results.Of 1,038 PUPs with severe hemophilia A, 930 (89.6%) were followed until 75 EDs, 429 until 500 EDs and 212 until 1000 EDs. In total, 300 inhibitors developed, of which 298 (99.3%) within the first 75 EDs. Thereafter only two inhibitors developed, both low titer: after 249 and 264 EDs. Conclusion.Almost all inhibitors develop during the first 75 EDs. Patients with severe hemophilia A can be defined as PTP after 75 instead of 150 exposure days. A change of definition of PTP will increase the number of severe hemophilia A patients eligible for new therapies. Disclosures Santagostino: Bioverativ: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees. Male:SOBI: Speakers Bureau; Shire: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Speakers Bureau; Novo Nordisk: Speakers Bureau; Biotest: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Oldenburg:Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Liesner:Baxalta: Consultancy, Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Sobi: Speakers Bureau; Bayer: Consultancy, Research Funding; Roche: Research Funding; Octapharma: Consultancy, Other: Clinical study investigator for NuProtect Study (Octapharma sponsored), Research Funding, Speakers Bureau. Carcao:Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL-Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; LFB: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nolan:CSL Behring: Research Funding; Sobi: Research Funding; Bayer: Research Funding. Álvarez-Roman:Shire: Consultancy; NovoNordisk: Consultancy; SOBI: Consultancy. Koenigs:Gilead: Research Funding; CSL Behring: Consultancy, Research Funding; Pfizer: Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Intersero: Research Funding; Bioverativ: Consultancy; Roche/Chugai: Consultancy; EU (IMI, FP7): Research Funding; Sobi: Consultancy, Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding; Novo Nordisk: Consultancy, Speakers Bureau; Biotest: Research Funding, Speakers Bureau; Jansen: Research Funding.
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Rodger, Marc, Johanna IP de Vries, Evelyne Rey, et al. "Low Molecular Weight Heparin for Prevention of Placenta-Mediated Pregnancy Complications: An Individual Patient Data Meta-Analysis." Blood 126, no. 23 (2015): 890. http://dx.doi.org/10.1182/blood.v126.23.890.890.
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Abstract Introduction Placenta-mediated pregnancy complications (PMPC) include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age (SGA) newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality. Affected women are at an elevated risk of recurrence in subsequent pregnancies. We completed a pooled summary-based (i.e. study level) meta-analysis that strongly suggests that low-molecular-weight heparin (LMWH) reduces the risk of recurrent PMPCs. However, our study-level meta-analysis was limited by high clinical and statistical heterogeneity likely due to the inclusion of women with heterogeneous prior PMPCs and trial designs (e.g. single vs multi-center trials). To address these limitations, the trialists agreed to conduct an individual patient data meta-analysis to identify sources of heterogeneity including exploring which patients benefit from LMWH and which outcomes are prevented. Methods We conducted a systematic review to identify randomised controlled trials that were eligible to contribute individual patient data to a meta-analysis to evaluate the effectiveness of LMWH for reducing the risk of PMPC in women with prior PMPCs. The primary outcome was a composite of early-onset or severe pre-eclampsia, birth of an SGA newborn < 5th percentile, late pregnancy loss (> 20 weeks), or placental abruption leading to delivery. Individual patient data from eligible women were re-coded in a prescribed format and combined in a common dataset for analysis. All studies were assessed for risk of bias. Results Data from 1049 women in nine trials were analysed; Participants were mostly Caucasian (88%) with a mean age of 31.518 had thrombophilia. 525 women were randomised to LMWH and 524 to no LMWH. In our primary outcome analysis, LMWH did not significantly reduce the risk of recurrent PMPCs (LMWH 60/459 (13.1%) vs. no LMWH 92/449 (20.5%) p=0.1). Significant heterogeneity was noted between single center and multi-center trials. In multi-center trials, LMWH reduced HELLP (p=0.03) but none of the other secondary outcomes, whereas in single center trials LMWH reduced all of the secondary outcomes. In sub-group analysis, in multi-center trials LMWH reduced the primary outcome in women with prior abruption (p<0.01) but none of the other sub-groups, whereas in single center trials LMWH was beneficial in all the sub-groups (prior pre-eclampsia, prior severe pre-eclampsia, prior early onset pre-eclampsia, prior SGA <10th, prior SGA < 5th and prior abruption). Conclusions In this individual patient data meta-analysis, LMWH does not appear to reduce the risk of recurrent PMPC in women with prior PMPC. Promising results suggest that women with prior abruption may benefit from LMWH but this should be replicated in future multi-center trials. PROSPERO registration:CRD42013006249 Table. Primary Analysis All Studies Multi-Center Studies Single Center Studies Composite outcome Risk difference (95% CI) N=908 -0.07 (-0.16, 0.01)p = 0.10 N=524 -0.01 (-0.11, 0.09) p = 0.89 N=384 -0.17 (-0.21, -0.13) p < .0001 Secondary Outcome Analyses Severe or Early Preeclampsia Risk difference (95% CI) N=946 -0.04 (-0.10, 0.02) p = 0.20 N=562 0.01 (-0.06, 0.07) p = 0.81 N=384 -0.11 (-0.16, -0.07) p <.0001 HELLP Risk difference (95% CI) N=813 -0.02 (-0.04, -0.004) p = 0.01 N=429 -0.01 (-0.02, -0.001) p = 0.03 N=384 -0.04 (-0.07, -0.01) p = 0.02 SGA <10 Risk difference (95% CI) N=913 -0.08 (-0.14, -0.02) p = 0.01 N=529 -0.03 (-0.10, 0.03) p = 0.32 N=384 -0.14 (-0.18, -0.10) p <0.0001 Abruption leading to delivery Risk difference (95% CI) N=945 -0.01 (-0.02, 0.003) p = 0.14 N=561 -0.01 (-0.03, 0.01) p = 0.53 N=384 -0.016 (-0.027, -0.005) p = 0.005 Subgroup Analyses Prior preeclampsia Risk difference (95% CI) N=583 -0.12 (-0.19, -0.04) p = 0.002 N=288 -0.06 (-0.19, 0.06) p = 0.34 N=295 -0.17 (-0.24, -0.11) p <.0001 Prior severe or early onset Preeclampsia Risk difference (95% CI) N=487 -0.10 (-0.19, -0.02) p = 0.02 N=236 -0.04 (-0.19, 0.12) p = 0.65 N=251 -0.17 (-0.23, -0.11) p <.0001 Any prior late loss (2 >12 weeks or 1 >16 weeks) Risk difference (95% CI) N=245 0.001 (-0.11, 0.12) p = 0.98 N=0 Prior SGA < 10 Risk difference (95% CI) N=305 -0.12 (-0.25, 0.01) p = 0.08 N=203 -0.03 (-0.17, 0.10) p = 0.64 N=102 -0.29 (-0.38, -0.20) p <.0001 Prior abruption Risk difference (95% CI) N=281 -0.16 (-0.22, -0.11) p <.0001 N=95 -0.13 (-0.22, -0.04) p = 0.01 N=186 -0.18 (-0.22, -0.14) p <.0001 Disclosures Rodger: Biomerieux: Honoraria, Research Funding. Off Label Use: Low Molecular Weight Heparin to prevent pregnancy complications. de Vries:Pfizer: Research Funding. Rey:Leo Pharma: Other: Travel Grant. Gris:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Stago: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Leo Pharma: Consultancy, Speakers Bureau; LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Research Funding; BI: Speakers Bureau; Bayer: Speakers Bureau; BMS: Speakers Bureau. Schleussner:Bayer: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Merck: Research Funding, Speakers Bureau. Middeldorp:GSK/Aspen: Research Funding; Bayer: Consultancy, Speakers Bureau; BI: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Daiichi-Sankyo: Consultancy, Speakers Bureau. Bates:Eli Lilly Canada: Other: I hold the Eli Lilly Canada/May Cohen Chair in Women's Health. Eli Lilly Canada provides unrestricted funding for partial salary support through this Chair. Eli Lilly Canada does not manufacture/distribute drugs relevant to the topic to be discussed..
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Junaedi, Akhmad. "PENGARUH RENUMERASI DAN ETOS KERJA TERHADAP KINERJA PEGAWAI PADA BIRO UMUM SEKRETARIAT UTAMA BADAN PUSAT STATISTIK." Majalah Ilmiah Bijak 14, no. 1 (2018): 48–59. http://dx.doi.org/10.31334/bijak.v14i1.59.
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The problem faced by the Central Bureau of Statistics is the remuneration that becomes the dependency of employees and the low work ethic. The problem causes employee performance is not optimal. This research uses quantitative analysis method with simple regression analysis tool, and multiple linear regression. The technique used in this research to obtain data about, is as follows: Interview and Questionnaire / Quesioner. The population of this study is all employees at the Central Bureau of Statistics (BPS), which amounts to 100 people including the Head of Public Bureau. Census sampling technique with sample random sampling and the result of formula used to determine and sampling by Taro Yamane (in Riduwan, 2010: 249). Data analysis using linear regression analysis using SPSS statistical test to see the effect of remuneration and work ethic on Performance of State Civil Apparatus (ASN) at General Bureau of Statistics Center in 2016, with significant 10%.After passing the validity and reliability of the data, obtained the result that states that Remuneration partially affect on employee performance. Similarly, work ethics based on research shows a significant effect on employee performance. Based on the results of the study and research together Remuneration and Working Ethics have a positive and significant impact on Employee Performance on the General Bureau of the Central Bureau of Statistics. Central Bureau of Statistics General Bureau. The regression equation is: Y = 22,917 + 0,123 X1 + 518X2, where every increase of 1 score of variable X1 (remuneration) and X2 (work ethic) will increase employee performance equal to 0,123, and 0,518, assuming other variable is constant,
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Takahashi, Naoto, Masahiro Kizaki, Masatomo Miura, et al. "Efficacy and Safety of Tyrosine Kinase Inhibitors for Treatment of Newly Diagnosed Chronic Myeloid Leukemia: Results Using Data Obtained with the New Target System from the Japanese Registry." Blood 132, Supplement 1 (2018): 1751. http://dx.doi.org/10.1182/blood-2018-99-111680.
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Abstract A multicenter observational study, conducted by the Japanese Society of Hematology (JSH), evaluated the effectiveness and safety of tyrosine kinase inhibitors (TKIs) in newly diagnosed patients with chronic myeloid leukemia -chronic phase (CML-CP). The clinical data of this study were collected using the New Target system, which is an online database that can be easily accessed by physicians. A total of 506 patients were enrolled from 102 institutions between April 2010 and March 2013; data for 444 patients (median age: 56 [range 18-92] years; 65% male) were analyzed. According to the Sokal score, 201 (45.3%), 178 (40.1%), and 64 patients (14.4%) were classified into the low, intermediate, and high-risk groups. As the first-line therapy, 148 (29.8%) patients received imatinib (IM), 173 (34.8%) received nilotinib (NIL), and 146 (29.4%) received dasatinib (DAS). BCR-ABL1 % was regularly monitored every 3 months in the first year and every 6 months thereafter. TKI plasma trough concentrations were determined with LC-MS/MS at 3, 6, and 12 months. At 60 months of follow up, 5-year progression-free survival (PFS) and overall survival (OS) were 94.5% (95%CI, 91.2-96.5) and 94.8% (95%CI, 91.6-96.9), respectively. The 5-year OS curve was significantly better in patients treated with NIL or DAS than that in patients with IM (IM, 90.9% [95%CI, 83.7-95.0]; NIL, 98.0% [95%CI, 92.2-99.5]; DAS, 96.0% [95%CI, 89.4-98.5]; log-rank test: P =0.0345). An early molecular response (EMR; BCR-ABL1 <10%) was found in 328 patients at 3 months (IM, n=84; NIL, n=127; and DAS, n=117). The 5-year PFS curve was significantly better in patients with EMR than without (EMR, 95.9% [95%CI, 92.6-97.7]; no-EMR, 77.5% [95%CI, 59.8-88.1]; log-rank test: P =0.0002). Additionally, 49 patients (IM, n=9; NIL, n=24; DAS, n=16) achieved deep molecular response (DMR; BCR-ABL1≤0.0032%) by 36 months. The DMR was observed in a higher proportion of patients with EMR (BCR-ABL1<10% at 3 months or BCR-ABL1<1% at 6 months) after TKI treatment (<10%, P =0.0367; <1%, P =0.0068). Testing for BCR-ABL1mutation was performed in 101 patients. Various BCR-ABL1mutations were identified in 23 patients (IM, n=13; NIL, n=8; and DAS, n=2). T315I mutation was not identified. Exon 8/9 35bp insertion was identified in 14 patients (IM, n=8; NIL, n=5; DAS, n=1). Seven out of these 14 patients achieved DMR; and all patients with exon 8/9 35bp insertion did not progress to accelerated or blast phase . The achievement of major molecular response (MMR, BCR-ABL1<0.1%) was associated with a higher trough concentration (C0) (DAS mean C02.65 ng/mL in MMR at 6 months vs. 1.98 ng/mL in no-MMR, P=0.0165; NIL mean C0 1,285.3 ng/mL in MMR at 3 months vs. 1,049.8 ng/mL in no-MMR,P=0.0746). No new safety issues occurred. Among 444 analyzed patients in the safety data set, only 2 patients with NIL had peripheral arterial occlusive disease [grade 1] or acute coronary disease [grade 3]. No patients developed pulmonary arterial hypertension in this study. We measured pleural effusion (PE) in patients with DAS and liver/pancreas dysfunction in patients with NIL, which were the common adverse events. In the DAS arm, 28 patients revealed pleural effusion (grade 1, 3 patients; grade2, 22 patients; grade3, 3 patients). It occurred not only in the first year of treatment but also in the second or third year (median 10.5 [range 1-60] months). However, no statistically significant association was found between pleural effusion and trough concentration of DAS in this study (2.71 ng/mL in patients with PE vs. 2.27 ng/mL in patients without, P =0.1339). In the NIL arm, 17 patients revealed severe liver dysfunction (grade 3-4, n=6), increased bilirubin values (grade 3, n=4), or increased lipase values (grade 3-4, n=7). The adverse events occurred in 3 months in these patients with NIL, except for 4 patients. In summary, this 5-year Japanese registry using the New Target system demonstrated that TKI treatments in newly diagnosed patients with CML-CP achieved satisfying and trustworthy outcomes. Figure. Figure. Disclosures Takahashi: Bristol-Myers Squibb: Research Funding, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Kizaki:Nippon Shinyaku,: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau. Kawaguchi:Novartis Pharma K.K.: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau. Suzuki:Celgene: Honoraria; Sawai Pharmaceutical: Honoraria; Ohtsuka: Honoraria; MSD: Research Funding; Meiji Seika Pharma: Honoraria; Takeda Pharmaceuticals: Honoraria; Shionogi: Honoraria; Novartis: Honoraria; Mochida Pharmaceutical: Honoraria; Chugai Pharmaceutical: Honoraria; Kyowa-Hakko Kirin: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Gilead Sciences: Consultancy; MundiPharma: Consultancy; Jazz Pharmaceuticals: Consultancy. Yamamoto:Chugai: Consultancy, Honoraria, Research Funding; Meiji Seika Pharma: Consultancy; Mundipharma: Consultancy, Honoraria; Ono: Consultancy, Honoraria, Research Funding; ARIAD Pharmaceuticals: Research Funding; Bayer: Research Funding; Celgene: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Gilead Sciences: Research Funding; MSD: Research Funding; Novartis: Honoraria, Research Funding; Solasia Pharma: Research Funding; SymBio: Research Funding; Takeda: Honoraria, Research Funding; AbbVie: Research Funding; Boehringer Ingelheim: Consultancy; Zenyaku: Research Funding; Bristol-Myers Squibb: Honoraria; Kyowa Hakko Kirin: Honoraria; Otsuka: Honoraria; Pfizer: Honoraria; Sumitomo Dainippon: Honoraria; HUYA: Honoraria. Naoe:Nippon Shinyaku Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Fujifilm Corporation: Patents & Royalties, Research Funding; Pfizer Japan Inc.: Research Funding; Astellas Pharma Inc.: Research Funding; Toyama Chemical Co., Ltd.: Research Funding. Akashi:MSD: Research Funding; Ono Pharmaceutical: Research Funding; Novartis pharma: Research Funding; Otsuka Pharmaceutical: Research Funding; Chugai Pharma: Research Funding; Astellas Pharma: Research Funding; Eisai: Research Funding; Taiho Pharmaceutical: Research Funding; sanofi: Research Funding; Asahi-kasei: Research Funding; Pfizer: Research Funding; Kyowa Hakko Kirin: Research Funding, Speakers Bureau; Eli Lilly Japan: Research Funding; Celgene: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau.
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von Drygalski, Annette, Adam Giermasz, Giancarlo Castaman, et al. "Etranacogene Dezaparvovec (AAV5-Padua hFIX variant), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate-Severe Hemophilia B: Two Year Data from a Phase 2b Trial." Blood 136, Supplement 1 (2020): 13. http://dx.doi.org/10.1182/blood-2020-139295.
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Background: Gene therapy for hemophilia offers the possibility to ameliorate disease severity to a mild or functionally curative state through a single administration. Etranacogene dezaparvovec (AMT-061) is an investigational gene therapy for hemophilia B comprising an adeno associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with liver specific promoter. Aims: We have previously shown a single dose of etranacogene dezaparvovec to provide sustained FIX activity into the mild-to normal range for up to 52 weeks post-dose in participants with severe or moderate-severe hemophilia B. This time, 2 years of follow-up data will be presented for the first time. Methods: A Phase 2b, open-label, single-dose, single-arm, multi-center trial (NCT03489291) in adult hemophilia B subjects. Interestingly, participants were not excluded based on neutralizing antibodies to AAV5. All subjects received a single intravenous dose of etranacogene dezaparvovec (2x1013 gc/kg) and will be followed for 5-years. The primary endpoint was FIX activity at Week 6. Secondary endpoints include e-diary recordings of bleeds and FIX concentrate use, laboratory parameters, joint health, patient reported outcomes, and adverse events (AEs). Results: All participants had FIX ≤1% (severe or moderately-severe FIX deficiency), required routine FIX prophylaxis, and had neutralizing activity to AAV5 at baseline. Following AMT-061 treatment, FIX activity increased rapidly to a mean of 31% at Week 6. At Week 52, mean FIX activity increased further to 41% with FIX activity levels of 50%, 31% and 41% in participants 1-3 respectively. There was no relationship between the presence of anti-AAV5 NAbs and response to etranacogene dezaparvovec. As of 52 weeks, there were no bleeds post-treatment and no requirement for FIX replacement aside from protocol-specified use for perioperative management in participant 3. There were no clinically significant elevations in liver enzymes and no participants required steroids related to the treatment. One participant experienced 2 mild AEs possibly related to treatment shortly after dosing (self-limiting headache and slightly elevated CRP). One patient had hip surgery due to worsening of pre-existing avascular necrosis deemed unrelated by investigator to etranacogene dezaparvovec and received FIX per protocol according to standard clinical practice. No participant developed inhibitors to FIX. Updated results to 2 years of follow-up will be presented with the main focus on FIX activity, FIX replacement therapy use and reported bleeds. Conclusions: Patients with AAV5 NAbs were included in the Phase 2b etranacogene dezaparvovec trial and have shown sustained FIX activity into the mild-to normal range. All participants were able to discontinue routine prophylaxis, and there have been no bleeds post-treatment with etranacogene dezaparvovec. Disclosures Giermasz: BioMarin: Consultancy, Research Funding, Speakers Bureau; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau; uniQure: Consultancy, Research Funding; Sangamo Therapeutics: Research Funding; Bioverativ/Sanofi: Consultancy, Research Funding, Speakers Bureau. Castaman:Alexion: Honoraria; Roche: Consultancy, Honoraria, Speakers Bureau; CSL Behring: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Ablynx: Honoraria; Baxalta/Shire: Honoraria; Bayer: Honoraria; Uniqure: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kedrion: Speakers Bureau; Werfen: Speakers Bureau; Sobi: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau. Key:Novo Nordisk: Other: Chair of Grants Committee; Takeda: Research Funding; Grifols: Research Funding; Uniqure: Consultancy. Miesbach:Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BioMarin Pharmaceutical Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; UniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Recht:Spark: Research Funding; Novo Nordisk: Consultancy, Other: personal fees, Research Funding; uniQure: Consultancy, Other: personal fees, Research Funding; Takeda: Consultancy, Other: personal fees, Research Funding; BioMarin: Research Funding; Pfizer: Consultancy, Other: personal fees; Genentech: Consultancy, Other: personal fees, Research Funding; CSL Behring: Consultancy, Other: personal fees. Gomez:Global Blood Therapeutics: Speakers Bureau. Gut:uniQure: Current Employment. Pipe:Siemens: Research Funding; Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees; Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy. OffLabel Disclosure: Etranacogene dezaparvovec (AMT-061) is an investigational gene therapy for hemophilia B comprising an adeno associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with liver specific promoter.
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Kandane-Rathnayake, R., W. Louthrenoo, A. Hoi, et al. "POS0028 DEFINING THE PREVALENCE OF UNMET NEED IN SLE: DATA FROM A LARGE MULTINATIONAL LONGITUDINAL SLE COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 218–19. http://dx.doi.org/10.1136/annrheumdis-2021-eular.938.
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Background:The recent prospectively validated definition of the lupus low disease activity state (LLDAS) allows characterisation of patients not achieving a treatment goal, providing impetus for an analysis of unmet needs in SLE using formal definitions. Other recently described definitions of high disease burden include disease activity over time, high disease activity status (HDAS) episodes, and the combination of high disease activity, serological activity and glucocorticoid (GC) use (HDAS+SA+GC).Objectives:To determine the prevalence of formal categories of unmet need, and the association of these with adverse outcomes, in SLE.Methods:Data from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected between 2013 and 19 using standard templates. Unmet need was defined as (i) patients never attaining LLDAS defined as in Golder et al., 2019 [1], (ii) having persistently active disease (time adjusted mean SLEDAI-2K (AMS) > 4), (iii) ever exhibiting high disease activity status (HDAS; SLEDAI-2K ≥10[2]), or (iv) ever exhibiting all of SLEDAI≥10, serological activity, and glucocorticoid use (HDAS+SA+GC)[3]. Health-related quality of life (HRQoL) was assessed using SF36 (v2) surveys and damage accrual using SLE Damage Index (SDI).Results:3,384 SLE patients were followed for 30,313 visits over median [IQR] 2.4 [0.4, 4.3] years. 53% of all visits were not in LLDAS; 813 patients (24%) never achieved LLDAS during observation. Median AMS was 3.0 [1.4, 4.9] and 34% of patients had AMS > 4 throughout the study. 25% of patients had at least one episode of HDAS, representing 8% of visits. 702 patients (21%) had at least one episode of HDAS+SA+GC, representing 8% of visits. Each of never-LLDAS, AMS>4, ever-HDAS, and ever-HDAS+SA+GC were associated with significantly greater number of physician visits, higher mean glucocorticoid dose, lower HRQoL and higher mortality. 31%, 58% and 83% of never-LLDAS, AMS>4, and ever-HDAS patients respectively were also HDAS+SA+GC on at least one occasion.Conclusion:Data from a multinational longitudinal SLE cohort indicate that unmet need, defined by LLDAS-never, AMS>4, HDAS, or HDAS+SA+GC, is prevalent in SLE, and that these definitions are associated with poor outcomes.References:[1]Golder, V., et al., Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.[2]Koelmeyer, R., et al., High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus Sci Med, 2020. 7(1).[3]van Vollenhoven, R.F., et al., Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Annals of the Rheumatic Diseases, 2012. 71(8): p. 1343-1349.Acknowledgements:The APLC acknowledges all the Data Collectors and Patients for their valuable contributions to research.Disclosure of Interests:Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Alberta Hoi Consultant of: Abbvie and GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Vera Golder: None declared, Yi-Hsing Chen Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Grant/research support from: Pfizer, Norvatis, BMS, Abbevie, Johnson & Johnson, Roche, Sanofi, Guigai, Roche, Boehringer Ingelheim, UCB, MSD, Astra-Zeneca, Astellas, Gilead, Shue Fen Luo: None declared, Yeong-Jian Jan Wu Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, Aisha Lateef: None declared, Jiacai Cho: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Abbot, Chak Sing Lau Shareholder of: Pfizer, Sanofi, and Janssen, Sandra Navarra Speakers bureau: Pfizer, Johnson & Johnson, Novartis, Astellas, Grant/research support from: Astellas, Johnson & Johnson, Leonid Zamora: None declared, Zhanguo Li Speakers bureau: Eli, Lilly, Novartis, GSK, AbbVie, Paid instructor for: Pfizer, Roche, Johnson., Consultant of: Lilly, Pfizer, Grant/research support from: Pfizer, Yuan An: None declared, Sargunan Sockalingam Speakers bureau: Pfizer, Roche, Novartis, Grant/research support from: Roche and Novartis, Yasuhiro Katsumata Speakers bureau: Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., and Sanofi K.K., masayoshi harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang Speakers bureau: Norvatis, GSK, Pfizer, Jun Kikuchi: None declared, Tsutomu Takeuchi Speakers bureau: AbbVie AYUMI Pharmaceutical Corp. Bristol-Myers Squibb Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan, Gilead Sciences, Inc. Mitsubishi-Tanabe Pharma Corp. Pfizer Japan Inc. Sanofi K.K., Consultant of: Astellas Pharma, Inc. Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Grant/research support from: AbbVie, Asahikasei Pharma Corp. Chugai Pharmaceutical Co, Ltd. Mitsubishi-Tanabe Pharma Corp. Sanofi K.K., BMDB Basnayake: None declared, Fiona Goldblatt: None declared, Madelynn Chan Speakers bureau: AbbVie, Novartis, Consultant of: Pfizer, Eli-Lilly, Kristine Ng Speakers bureau: Abbvie, Novartis, Janssen, Sang-Cheol Bae: None declared, Shereen Oon: None declared, Sean O’Neill Consultant of: GSK, Kathryn Gibson Speakers bureau: UCB, Consultant of: Novartis, Janssen, Grant/research support from: Novartis, Sunil Kumar: None declared, Nicola Tugnet: None declared, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, Grant/research support from: Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Eric F. Morand Speakers bureau: AstraZeneca, Paid instructor for: Eli Lilly, Consultant of: AstraZeneca, Amgen, Biogen, BristolMyersSquibb, Eli Lilly, EMD Serono, Genentech, Janssen, Grant/research support from: AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, Janssen.
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Richardson, Paul G., Sagar Lonial, Andrzej J. Jakubowiak, et al. "High Response Rates and Encouraging Time-to-Event Data with Lenalidomide, Bortezomib, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Final Results of a Phase I/II Study." Blood 114, no. 22 (2009): 1218. http://dx.doi.org/10.1182/blood.v114.22.1218.1218.
Full textAbstract:
Abstract Abstract 1218 Poster Board I-240 Background The combination of lenalidomide (Len, Revlimid®), bortezomib (Bz, Velcade®), and dexamethasone (dex; RVD) has shown excellent efficacy in relapsed/refractory multiple myeloma (MM) patients, with overall response rates (ORR; ≥partial response [PR]) of 69%, including 26% complete/near complete responses (CR/nCR), and manageable toxicities (Anderson et al. ASCO 2009). The phase I portion of the study (Richardson et al. IMW 2009) found the maximum tolerated dose (MTD) of this combination in newly diagnosed MM patients to be Len 25 mg/day, Bz 1.3 mg/m2, and dex 20 mg. In all phase I patients, the ORR was 100%, including 31% CR, 9% nCR, and 75% 3very good PR (VGPR). Results reported here are for patients treated in the phase II portion of the study. Methods Patients were treated with Len 25 mg/day (days 1–14), Bz 1.3 mg/m2 (days 1, 4, 8, 11), and dex 20 mg (cycles 1–4) and 10 mg (cycles 5–8) on the day of and day after Bz for up to eight 21-day cycles. Patients received prophylactic anticoagulants. Responses were assessed by modified EBMT and Uniform criteria to include nCR and VGPR. Patients with at least PR could proceed to ASCT after 34 cycles; responding patients who did not go on to ASCT could continue therapy at their physician's discretion. Patients with 3grade 2 peripheral neuropathy (PNY) by CTCAE v3 were excluded. Thirty five patients were enrolled in the phase II portion of this study and were evaluable for both efficacy and safety. Results Median age was 59 years (range 22-86), 54% were men, 34% / 54% / 11% were ISS Stage I / II / III, and 57% / 31% had IgG / IgA MM, respectively. Patients received a median of 8 cycles of Bz and dex and 11 cycles of Len; 11 (31%) patients remain on therapy. Among the 24 patients who have gone off therapy, 5 (21%) completed treatment per protocol, 8 (33%) proceeded to ASCT, 3 (13%) had progressive disease (all during cycle 14 or later), 1 (4%) withdrew due to toxicities, 1 (4%) received non-protocol therapy, and the remaining (n=6; 25%) withdrew consent or stopped treatment due to physician decision. All patients (100%) had a best confirmed pre-ASCT response of 3PR, with 54% CR/nCR and 69% 3VGPR (Table). Response rates in the 31 and 24 patients who completed 4 and 8 cycles, respectively, are shown in the Table. Among the 24 patients without CR at cycle 4, response improved between cycles 4 and 8 in 16 (67%) patients. Fifteen of the 35 (43%) patients were mobilized for ASCT, with a median stem cell yield of 4.4 × 106 (2.3–6.6 × 106) CD34+ cells/kg. After median follow-up of 19.3 months, median time to progression (TTP), progression-free survival (PFS), and overall survival (OS) have not been reached; the estimated 1-year TTP and PFS are 76% and the estimated OS is 100%. Treatment-emergent grade 3 and 4 adverse events that occurred in >1 patient included lymphopenia (n=7; 20%), hypokalemia (n=3; 9%), and fatigue and neutropenia (n=2; 6% each). Sensory PNY of any grade occurred in 27 (77%) patients, which was grade 1 (n=18; 67%) and grade 2 (n=8; 30%) in the majority of patients; only one patient had grade 3 sensory PNY. Neuropathic pain and motor PNY were reported in 10 (29%; all grade 1 and 2) and 6 (17%; 1 grade 3) patients, respectively, with no grade 3 PNY seen. Importantly, PNY was reversible with dose reduction, supportive care, and/or completion of therapy. Thrombosis/thromboembolism was reported in just 2 (6%) patients. No treatment-related mortality was seen. Conclusion These phase II results suggest that RVD is a highly effective combination, with a pre-ASCT ORR of 100% and high rates of CR/nCR, and encouraging time-to-event analyses to date. RVD was well tolerated, with limited rates of grade 3 PNY and DVT/PE despite prolonged use of Bz and Len. Data from patients treated at the MTD in phase I and the impact of adverse risk factors (including advanced stage and high-risk cytogenetics) on outcome, as well as following ASCT, will be reported at the meeting. Based upon these promising results, phase II/III studies of RVD and RVD-based combinations are either planned or ongoing. Disclosures Richardson: Keryx: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Lonial:BMS: Consultancy; Gloucester: Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy. Jakubowiak:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Exelixis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Centocor Ortho Biotech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers-Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jagannath:Merck: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria. Raje:AstraZeneca: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Ghobrial:Millennium Pharmaceuticals, Inc.: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Speakers Bureau. Schlossman:Millennium Pharmaceuticals, Inc.: Speakers Bureau; Celgene: Speakers Bureau. Mazumder:Millennium Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Munshi:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Laubach:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vesole:Celgene: Consultancy, Equity Ownership. Rosenblatt:Celgene: Research Funding. Doss:Millennium Pharmaceuticals, Inc.: Speakers Bureau; Celgene: Speakers Bureau. Mitsiades:Millennium Pharmaceuticals, Inc.: Consultancy; Novartis Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy; Merck & Co.: Consultancy; Kosan Pharmaceuticals: Consultancy; Pharmion: Consultancy; Amgen Pharmaceuticals: Research Funding; AVEO Pharma: Research Funding; EMD Serono: Research Funding; Sunesis Pharmaceuticals: Research Funding; PharmaMar: Licensing royalties. Hideshima:Biotest AG: Consultancy. Knight:Celgene: Employment, Equity Ownership. Esseltine:Millennium Pharmaceuticals, Inc.: Employment, Equity Ownership. Anderson:Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding.
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Zinzani, Pier Luigi, Armando Santoro, Luigina Mollica, et al. "Copanlisib, a PI3K Inhibitor, Demonstrates a Favorable Long-Term Safety Profile in a Pooled Analysis of Patients with Hematologic Malignancies." Blood 134, Supplement_1 (2019): 4009. http://dx.doi.org/10.1182/blood-2019-131779.
Full textAbstract:
Introduction: Copanlisib, a pan-class I phosphatidylinositol 3-kinase inhibitor, is approved in the US for the treatment of patients (pts) with relapsed follicular lymphoma (FL) who have received ≥2 prior systemic therapies; it also has Breakthrough Therapy designation for pts with relapsed marginal zone lymphoma who have received ≥2 prior therapies. The Phase II CHRONOS-1 study in pts with indolent lymphoma treated with copanlisib (NCT01660451; Part B) demonstrated an objective response rate of 59.2% with manageable safety and low rates of severe adverse events (AEs) (Dreyling M et al. J Clin Oncol 2017). We report pooled safety data from 8 Phase I and II studies of pts with hematologic malignancies following long-term treatment with copanlisib. Methods: Pts with hematologic malignancies treated with copanlisib monotherapy in completed open-label Phase I or II studies were included. Copanlisib 60 mg (i.v.) was administered intermittently on days (d) 1, 8, and 15 of a 28-d cycle until disease progression (PD) or unacceptable toxicity. AEs were reported using MedDRA (v.21.1) and assessed by time of onset (worst grade or new AEs occurring ≤180 d, 181-360 d, or ≥361 d) and treatment duration. Results: A total of 364 pts received copanlisib (data cut-off Feb 2019). Median age was 65 years (range 22-93); the predominant histology was FL (42.0%). At data cut-off, 34 pts (9.3%) remained on treatment. Duration of treatment ranged from 0.2 to 62.1 months, with 56 pts (15.4%) treated for >1 year. All-grade treatment-emergent AEs (TEAEs) were reported in 97.8% of pts; 51.4% had TEAEs of worst grade [g] 3, and 24.7% had TEAEs of worst g4. The most common (≥20%) TEAEs (all grade / g3 / g4) were hyperglycemia (50.5% / 28.3% / 4.4%), hypertension (38.7% / 29.1% / 0%), diarrhea (37.1% / 4.9% / 0%), nausea (28.3% / 1.4% / 0%), fatigue (27.2% / 2.7% / 0%), pyrexia (23.1% / 3.0% / 0%), and neutropenia (23.1% / 9.3% / 9.6%). Hyperglycemia and hypertension were infusion related, transient, and manageable. Events generally were reported early, with higher incidence at ≤180 d (n=364) vs 181-360 d (n=118) or ≥361 d (n=56), and no increased incidence of g≥3 events with prolonged exposure, with the exception of diarrhea (all grade [g≥3]): hyperglycemia (49.2% [31.6%] / 21.2% [11.0%] / 19.6% [10.7%]), hypertension (37.4% [27.2%] / 21.2% [15.3%] / 21.4% [17.9%]), diarrhea (32.7% [3.0%] / 20.3% [4.2%] / 30.4% [12.5%]), nausea (27.5% [1.4%] / 0.8% [0%] / 3.6% [0%]), fatigue (24.2% [2.5%] / 5.9% [0.8%] / 10.7% [1.8%]), pyrexia (19.2% [2.7%] / 16.1% [0.8%] / 10.7% [0%]), and neutropenia (19.5% [16.2%] / 13.6% [8.5%] / 21.4% [16.1%]). A similar trend was observed in pts treated for >1 year (Table), though these pts had a broad range of exposures, with 22 pts treated for ≥2 years. Incidences of g≥3 diarrhea in pts treated for >1 year remained stable and were comparable with prolonged exposure (≤180 d 8.9%; 181-360 d 7.1%; ≥361 d 12.5%). Pneumonitis was infrequent overall (all grade / g≥3: 5.2% / 2.7%) and in pts treated for >1 year (10.7% / 3.6%). Copanlisib-related TEAEs of all grades / g3 / g4 were reported for 88.7% / 54.1% / 18.4% of pts; most events were reported early (≤180 d) with generally no increase in incidence or severity observed in pts treated for >1 year. Serious AEs (SAEs) occurred in 57.1% of pts, most commonly (≥2%; all grade / g≥3) pneumonia (6.0% / 5.5%), general physical health deterioration (5.2% / 4.9%), pyrexia (4.1% / 1.4%), hyperglycemia (4.1% / 4.1%), pneumonitis (4.1% / 2.7%), lung infection (3.0% / 2.2%), and febrile neutropenia (2.2% / 2.2%). All-grade / g3 / g4 copanlisib-related SAEs were reported for 30.2% / 18.7% / 5.8% of pts. As with TEAEs, SAEs mostly occurred early with no general increase in incidence or severity with treatment >1 year. Thirty-nine pts died either during copanlisib treatment or within 35 d post discontinuation of treatment (10.7%), most commonly due to PD (4.7%). No g4 late-onset colitis, hepatotoxicity, or other intestinal toxicity occurred after 6 months of treatment. Conclusions: These data provide evidence for the manageable safety profile of long-term copanlisib treatment, with no late-onset toxicities or worsening of severity of TEAEs, and few severe gastrointestinal TEAEs. Transient, manageable hyperglycemia and hypertension were among the most common TEAEs; no new unexpected safety issues were identified. These results support the known safety profile and approved indication of copanlisib. Disclosures Zinzani: IMMUNE DESIGN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANOFI: Consultancy; CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PORTOLA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; VERASTEM: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Santoro:Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Takeda: Speakers Bureau; Abb-Vie: Speakers Bureau; Sandoz: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; MSD: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Roche: Speakers Bureau. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Follows:AZ: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Lenz:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Agios: Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Employment, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy. Kim:Celltrion: Research Funding; Mundipharma: Research Funding; J&J: Research Funding; Roche: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; Donga: Research Funding. Panayiotidis:Bayer: Other: Support of clinical trial. Demeter:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol- Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Angelini: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Morschhauser:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Munoz:Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Pharmacyclics LLC an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Kite Pharma: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Portola: Research Funding; Incyte: Research Funding. Miriyala:Bayer HealthCare Pharmaceuticals, Inc.: Employment. Benson:Bayer HealthCare Pharmaceuticals, Inc.: Employment. Garcia-Vargas:Bayer Healthcare Pharmaceuticals, Inc.: Employment. Childs:Bayer Healthcare Pharmaceuticals, Inc.: Employment. Dreyling:Novartis: Other: Scientific advisory board; Celgene: Other: Scientific advisory board, Research Funding, Speakers Bureau; Gilead: Other: Scientific advisory board, Speakers Bureau; Janssen: Other: Scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Other: Scientific advisory board, Research Funding; Roche: Other: Scientific advisory board, Research Funding, Speakers Bureau; Sandoz: Other: Scientific advisory board; Acerta: Other: Scientific advisory board; Bayer: Other: Scientific advisory board, Speakers Bureau. OffLabel Disclosure: Copanlisib is approved in the U.S. for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies and received U.S. FDA Breakthrough Designation in May 2019 for the treatment of adult patients with relapsed marginal zone lymphoma (MZL) who have received at least 2 prior therapies. We present here Phase I and II clinical trial data of patients with a range of hematological malignancies, including FL and MZL, treated with copanlisib.
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Li, Shan Shan, Tao Hao, and Zheng Yu Liang. "A Comprehensive Evaluation Method of Primary Frequency Regulation Based on Wide Area Measurement System Data." Applied Mechanics and Materials 672-674 (October 2014): 996–1000. http://dx.doi.org/10.4028/www.scientific.net/amm.672-674.996.
Full textAbstract:
On the basis of comparative research on primary frequency regulation (PFR) evaluation index of each grid bureau, a comprehensive evaluation index system of PFR is established, including some specific solution scheme according to problems existing in PFR evaluation index of Central China power grid bureau. The index system ensures a more precise and accurate evaluation of actual PFR process. Meanwhile, accurate data source is provided for correct calculation of PFR index through signals processing of wide area measurement system (WAMS) data.
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Isnardi, C. A., E. E. Civit De Garignani, A. García Ciccarelli, et al. "AB0214 SURVIVAL, EFFICACY AND SAFETY OF GOLIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND SPONDYLOARTHRITIS: DATA FROM AN ARGENTINEAN COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 1133–34. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1399.
Full textAbstract:
Background:Golimumab is a human monoclonal antibody directed against TNFα in its soluble and transmembrane forms. It can be used subcutaneously or intravenously and has shown efficacy for use in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS).Objectives:The aim of this study was to evaluate the efficacy, safety, and cumulative survival of golimumab in patients with RA, PsA and AS from different rheumatology centers in Argentina.Methods:We performed a longitudinal study of consecutive adults with RA (ACR/EULAR 2010 criteria), PsA (CASPAR criteria) and AS (ASAS 2009 criteria), who have started treatment with subcutaneous or intravenous golimumab according to medical indication in each center. Data was obtained by review of medical records. Sociodemographic and clinical data, musculoskeletal manifestations, comorbidities, previous treatments were recorded. In reference to golimumab treatment, start date, route of administration and concomitant treatments were identified. Disease activity was assessed using DAS28 for RA patients, DAPSA and MDA for PsA and BASDAI for AS. The presence of adverse events (AE) was recorded. If golimumab was stopped, date and cause was documented. Patients were followed up until golimumab discontinuation, loss of follow-up, or study completion (November 30, 2020). Statistical analysis: Chi2 test or Fischer exact test and T test or Mann Whitney and ANOVA or Kruskal Wallis, as appropriate. The incidence of EA was assessed in events every 100 patient/year. Kaplan-Meier curves and log Rank analysis. Cox proportional regression.Results:One hundred eighty two patients were included, 116 with a diagnosis of RA, 30 with PsA and 36 with AS. Most of them (70.9%) were female with a median (m) age of 55 years (IQR 43.8-64) and m disease duration of 7 years (IQR 4-12.7) at treatment initiation. Al least one prior biological DMARD or a small molecule was received by 63 patients (34.6%). The most frequent indication cause was conventional DMARD failure. In 94.8% of the patients Golimumab was administered subcutaneously, and in 80.8% in association with conventional DMARDs, the most frequently used was methotrexate. Total follow-up was 318.1 patients/year.Golimumab treatment showed clinical improvement in all three groups of patients. In RA patients DAS28 significantly decreased during the first 12 months of follow-up, m 5.9 (IQR 4.9-6.6) at baseline, 3.8 (IQR 2.6-4.6) at 6 months and 2.8 (IQR 2.1-3.6) at 12 months, p <0.0001. In PsA, m DAPSA-ESR value was 32.2 (IQR 24.2-47.7), 10.1 (IQR 5.8-18.3) and 11.2 (IQR 3.4-24) at baseline, 6 and 12 months, respectably (p <0.0001). In AS, m BASDAI was 6.2 (IQR 4.8-7.3), 2.8 (IQR 1.7-4.1) and 2.2 (IQR 1.1-3.2), at baseline, 6 and 12 months respectively (p <0.0001).The incidence of adverse events was 6.6 per 100 patients/year, being infections the most frequents ones. During follow-up, 50 patients (27.5%) discontinued golimumab, the most frequent cause was treatment failure (68%), followed by lack of health insurance (16%) and adverse events (10%). Golimumab persistence was 79% and 57.6% at 12 and 24 months, respectively. Treatment survival was 50.2 months (95% CI 44.4-55.9). Patients who had received prior treatment with biological DMARDs or small molecules showed lower survival (Figure 1). In the multivariate analysis, adjusting for age, sex and disease duration, those patients showed twice the risk of suspending treatment (HR 2.01, 95% CI 1.1-3.7).Figure 1.Golimumab survival according to prior b-DMARD o small molecule treatment.Conclusion:Golimumab treatment in real life patients in Argentina has shown good efficacy and safety. Drug survival was over 4 years and almost 80% were still using golimumab after one year. Prior treatment with other b-DMARDs o small molecules was associated with lower treatment survival.Disclosure of Interests:Carolina Ayelen Isnardi Speakers bureau: Bristol Myers Squibb, Janssen, Grant/research support from: Pfizer, Emma Estela Civit De Garignani Speakers bureau: Abbvie, Novartis, Agustín García Ciccarelli Speakers bureau: Janssen, Novartis, Consultant of: Novartis, Grant/research support from: Janssen, Novartis, Jimena Sanchez Alcover: None declared, Rodrigo Garcia Salinas Speakers bureau: Abbvie, AMGEN, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen Cilag, Montpellier-UCB, Novartis, Roche – Genentech, Sanofi, Merck Serono., Sebastian Magri Speakers bureau: Abbvie, AMGEN, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen Cilag, Montpellier-UCB, Novartis, Roche – Genentech, Sanofi, Merck Serono., Eduardo Albiero Consultant of: Janssen, Carla Gobbi Speakers bureau: Pfizer, Consultant of: Pfizer, Janssen, Edson Velozo Speakers bureau: Janssen, Novartis, Pfizer, Consultant of: Abbvie, Janssen, Novartis, Grant/research support from: Janssen, Novartis, Pfizer, Enrique Soriano Speakers bureau: AbbVie, Novartis, Bristol MS, Novartis, Eli Lilly, Genzyme, Pfizer, Amgen, and Roche, Consultant of: Novartis, AbbVie, Pfizer, Eli Lilly, Sanofi, Sandoz, Amgen., Grant/research support from: Roche, Novartis, AbbVie, Glaxo Smith Kline, BMS, Martín Brom: None declared, Johana Zacariaz Grant/research support from: Bristol Myers Squibb, Ingrid Strusberg Speakers bureau: Gema Biotech SAU, BMS, Abbvie, Consultant of: Gema Biotech SAU, Abbvie, Janssen, Grant/research support from: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Marcos BARAVALLE Speakers bureau: Montepellier, Consultant of: Abbvie, Janssen, Grant/research support from: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Sol Castaños Speakers bureau: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Liliana Morales Speakers bureau: Lilly, Consultant of: Janssen, Grant/research support from: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Sergio Paira: None declared, Romina Calvo: None declared, Alberto Ortiz: None declared, Rodolfo Perez Alamino Speakers bureau: Pfizer, Abbvie, Amgen, Bristol-Myers-Squibb, Lilly, Janssen, Novartis, Hernan Maldonado Ficco Speakers bureau: Pfizer, Abbvie, Jansen, Novartis, Bago, Bristol, Eli Lilly., Consultant of: Pfizer, Abbvie, Novartis, Jansen, Bago, Eli Lilly., Gustavo Citera Speakers bureau: Abbvie, BMS, Lilly, Jansen, Gema, Pfizer, Roche, Grant/research support from: Pfizer
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Hermans, Cedric, Claude Négrier, Pål A. Holme, et al. "Real-World Clinical Management of Patients with Congenital Hemophilia and Inhibitors: Interim Analysis of the FEIBA Global Outcome Study (FEIBA GO)." Blood 136, Supplement 1 (2020): 23–24. http://dx.doi.org/10.1182/blood-2020-139298.
Full textAbstract:
Introduction and Objective: Development of inhibitory antibodies is a major complication of factor replacement therapy in patients with congenital hemophilia A or B. The FEIBA Global Outcome study (FEIBA GO) assessed the long-term safety and real-world effectiveness of activated prothrombin complex concentrate (aPCC; Baxalta US Inc, a Takeda company, Lexington, MA, USA) as prophylaxis or on-demand treatment in patients with congenital hemophilia A or B with inhibitors (PwHI) across different clinical settings. Methods: FEIBA GO (EUPAS6691) is a post-authorization, prospective, observational, multicenter cohort study. Male PwHI diagnosed before study entry and prescribed treatment with aPCC as part of routine clinical practice were followed over 4 years; treatment regimens were prescribed at the physician's discretion. Ethics approval and patient consent were obtained. These data report on an interim analysis (data cutoff, May 16, 2019) on the annualized bleeding rate (ABR) calculated per patient-year of follow-up and aPCC consumption in patients receiving aPCC prophylaxis. Results: Enrollment was started on September 3, 2014 and completed on December 31, 2017. Fifty-one enrolled PwHI have received aPCC prophylaxis (n=37) or on-demand (n=14) treatment from 26 sites in 11 countries (hemophilia A: n=50, hemophilia B: n=1; median [range] age at baseline: 17 [2-71] years). As of May 2019, mean±SD (median, range) ABR was 7.2±8.2 (5.7, 0-30) per patient-year for the 14 patients with ≥2 to &lt;4 years' study follow-up (mean±SD: 3.0±0.6 years). In the 3 patients with ≥4 years of study follow-up (mean±SD: 4.0±0.03 years), mean±SD (median, range) ABR was 14.7±25.3 (0.2, 0-44) per patient-year. Patients received a variety of prophylaxis regimens; data on dosages per infusion and number of weekly infusions administered are provided in the Table. Conclusions: This interim analysis describes the real-world use and effectiveness of aPCC prophylaxis and supports previous data on the prevention of bleeding events in PwHI. The data also highlight the variety of dosing regimens reflecting the real-world use of aPCC prophylaxis in clinical practice. Although patient numbers were small, these data suggest that increased weekly doses are used in patients with more severe bleeding phenotypes. Figure 1 Disclosures Hermans: Kedrion:Speakers Bureau;Octapharma:Consultancy, Speakers Bureau;Roche:Consultancy, Speakers Bureau;Pfizer:Consultancy, Research Funding, Speakers Bureau;Novo Nordisk:Consultancy, Speakers Bureau;LFB:Consultancy, Speakers Bureau;Shire, a Takeda company:Consultancy, Research Funding, Speakers Bureau;Sobi:Consultancy, Research Funding, Speakers Bureau;Bayer:Consultancy, Research Funding, Speakers Bureau;EAHAD:Other;WFH:Other;CSL Behring:Consultancy, Speakers Bureau;CAF-DCF:Consultancy, Speakers Bureau;Biogen:Consultancy, Speakers Bureau.Négrier:CSL Behring, Octapharma, Shire/Takeda, Sobi:Research Funding;CSL, F. Hoffmann-La Roche Ltd, Sobi:Other: Travel support;Bayer, Biomarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Shire/Takeda, Sobi, Spark:Consultancy.Holme:Sobi:Honoraria, Research Funding;Bayer:Honoraria, Research Funding;CSL Behring:Honoraria;Novo Nordisk:Honoraria;Octapharma:Research Funding;Pfizer:Honoraria, Research Funding;Shire, a Takeda company:Honoraria, Research Funding.Escuriola:Grifols:Honoraria;CSL Behring:Consultancy, Honoraria, Research Funding;Biotest:Honoraria, Research Funding;Biomarin:Honoraria;Bayer:Honoraria;Kedrion:Honoraria;Shire, a Takeda company:Honoraria;Octapharma:Consultancy, Honoraria, Research Funding;Novo Nordisk:Consultancy, Honoraria;Roche:Honoraria;Sobi:Honoraria, Research Funding.Cid:Roche:Consultancy, Honoraria;Sobi:Consultancy, Honoraria;Novo Nordisk:Honoraria;Shire, a Takeda company:Honoraria.Kemenyash:Takeda Pharmaceutical International AG:Current Employment, Current equity holder in publicly-traded company.Botha:Takeda Pharmaceutical International AG:Current Employment, Current equity holder in publicly-traded company.Cano-Garcia:Sanofi Genzyme:Current Employment, Current equity holder in publicly-traded company;Shire, a Takeda company:Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months.Windyga:Sanofi:Honoraria, Research Funding;Alexion:Honoraria, Research Funding;Alnylam:Honoraria, Research Funding;Baxalta/Shire, a Takeda company:Honoraria, Research Funding;Bayer:Honoraria, Research Funding;Siemens:Honoraria, Research Funding;Sobi:Honoraria, Research Funding;Werfen:Honoraria, Research Funding;CSL Behring:Honoraria, Research Funding;Ferring Pharmaceuticals:Honoraria, Research Funding;Novo Nordisk:Honoraria, Research Funding;Octapharma:Honoraria, Research Funding;Rigel Pharmaceuticals:Honoraria, Research Funding;Roche:Honoraria, Research Funding.
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Pipe, Steven, Adam Giermasz, Giancarlo Castaman, et al. "One Year Data from a Phase 2b Trial of AMT-061 (AAV5-Padua hFIX variant), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate-Severe Hemophilia B." Blood 134, Supplement_1 (2019): 3348. http://dx.doi.org/10.1182/blood-2019-128765.
Full textAbstract:
Background: Gene therapy for hemophilia offers the possibility of ameliorating the disease severity to a milder or functionally curative state through a single treatment. AMT-061 is an investigational gene therapy for hemophilia B comprising an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with liver-specific promoter. Aims: Confirm that a single dose of AMT-061 will provide a minimum-therapeutic response of FIX activity 6-weeks post-dose in participants with severe or moderate-severe hemophilia B. Here, 1 year of follow-up will be presented for the first time. Methods: Phase 2b, open-label, multi-center trial (NCT03489291) in adult males with FIX ≤2% and without active hepatitis or uncontrolled HIV. Participants were not excluded based on neutralizing antibodies to AAV5. Participants received a single intravenous dose of AMT-061 (2x1013 gc/kg) and will be followed for 5-years. The primary endpoint was FIX activity at Week 6. Secondary endpoints include e-diary recordings of bleeds and FIX concentrate use, laboratory parameters, joint health, patient-reported outcomes, and adverse events (AEs). Results: All participants had FIX ≤1% (severe or moderately-severe FIX deficiency), required routine FIX prophylaxis, and had neutralizing activity to AAV5 at baseline. Following AMT-061 treatment, FIX activity increased rapidly (Figure) to a mean of 31% at Week 6. At Week 36, mean FIX activity increased further to 45% with FIX activity levels of 54%, 30% and 51% in participants 1-3 respectively. As of 36 weeks, there were no bleeds post-treatment and no requirement for FIX replacement aside from protocol-specified use for perioperative management in participant 3. There were no clinically significant elevations in liver enzymes and no participants required steroids related to the treatment. One participant experienced 2 mild AEs possibly related to treatment shortly after dosing (self-limiting headache and slightly elevated CRP). One patient had hip surgery due to worsening of pre-existing avascular necrosis deemed unrelated by investigator to AMT-061 and received FIX per protocol according to standard clinical practice. No participant developed inhibitors to FIX. Updated results to 52 weeks of follow-up will be presented. Conclusions: Sustained elevation of FIX activity into the mild-to-normative range were observed in all participants 36 weeks after treatment with AMT-061. AMT-061 was safe and well-tolerated with no requirement for immunosuppression. These data support the ongoing Phase 3 study. Figure Disclosures Pipe: Novo Nordisk: Consultancy; Apcintex: Consultancy; Roche/Genentech: Consultancy; BioMarin: Consultancy; Shire: Consultancy; Sanofi: Consultancy; uniQure: Consultancy; Pfizer: Consultancy; HEMA Biologics: Consultancy; Catalyst Bioscience: Consultancy; Freeline: Consultancy; CSL Behring: Consultancy; Bayer: Consultancy; Spark Therapeutics: Consultancy. Giermasz:Genentech/Roche: Consultancy, Other: Research, Speakers Bureau; Sangamo: Other: Research; BioMarin: Consultancy, Other: Research; uniQure: Consultancy, Other: Research; Bioverativ/Sanofi: Consultancy, Speakers Bureau. Castaman:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kedrion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda (SHIRE): Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Uniqure: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Werfen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Key:Uniqure BV: Research Funding. Leebeek:CSL Behring: Research Funding; Baxalta/Shire: Research Funding; uniQure BV: Consultancy, Research Funding. Miesbach:Bayer, Chugai, Novo Nordisk, Octapharma, Pfizer, Takeda/Shire, UniQure: Speakers Bureau; Bayer, BioMarin, CSL Behring, Chugai, Freeline, Novo Nordisk, Octapharma, Pfizer, Roche, Takeda/Shire, UniQure: Consultancy; Bayer, Novo Nordisk, Octapharma, Pfizer, Takeda/Shire: Research Funding. Recht:Bioverativ, CSL Behring, Genentech, Kedrion, NovoNordisk, Pfizer, Shire, Uniqure: Consultancy; American Thorombosis & Hemostasis Network: Other: Immediate Past Chair; Bioverativ, Genentech, NovoNordisk Shire: Research Funding. Gomez:Alnylam: Consultancy; Novo Nordisk, Novartis, Pfizer, Sanofi, Takeda, UniQure: Research Funding. Long:Uniqure BV: Employment. Gut:Uniqure BV: Employment. von Drygalski:University of California San Diego: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; UniQure, Bayer, Bioverativ/Sanofi, Pfizer, Novo Nordisk, Biomarin, Shire, CSL Behring: Consultancy; Hematherix Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Founder.
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Hohloch, Karin, Christine Windemuth-Kieselbach, Pier Luigi Zinzani, et al. "Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry." Blood 134, Supplement_1 (2019): 5263. http://dx.doi.org/10.1182/blood-2019-124192.
Full textAbstract:
To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy. Jurczak:Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.
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Gangadharan, Bagirath, Birgit M. Reipert, Verena Berg, et al. "Data Coming out of the Human Inhibitor PUP Study (HIPS) Reveal 4 Subgroups of Patients with Distinct Antibody Signatures." Blood 132, Supplement 1 (2018): 3774. http://dx.doi.org/10.1182/blood-2018-99-115979.
Full textAbstract:
Abstract Background and objectives FVIII inhibitors remain the major complication of replacement therapy in hemophilia A. Why some patients develop inhibitors whereas others do not is poorly understood. The Hemophilia Inhibitor PUP Study (HIPS, clinicaltrials.gov NCT01652027), a prospective multicenter observational study, aim to identify early immune biomarkers which predict inhibitor development in previously untreated patients (PUPs) with severe hemophilia A. Such biomarkers would facilitate early risk identification and the initiation of potential immune intervention strategies. Previously we reported time-resolved antibody data for the first 15 patients who completed antibody analysis (Gangadharan 2017). Here we present data from all 25 patients enrolled in HIPS, identifying four distinct patient subgroups based on their unique antibody signatures. We also summarize data for F8 mutations and longitudinal data of circulating immune cells such as FoxP3+ T cells (Tregs), Th17 cells, and granulysin+ cells. Methods FVIII inhibitor testing (Nijmegen method, performed in the central laboratory Medical University of Vienna) and antibody analytics were assessed prior to first exposure, 7-9 days after exposure day (ED) 1 and 5-7 days after EDs 5, 10, 20, 30, 40, and 50. FVIII-specific advanced antibody analytics were performed using methodology described by Whelan 2013 and Hofbauer 2015. FVIII mutational analysis was performed at Bloodworks Northwest, Seattle. Longitudinal epigenetic cell counting in whole blood using quantitative PCR-based methylation assays (www.epiontis.com) was done to monitor changes in peripheral FoxP3+ T cells (Tregs), pro-inflammatory Th17 cells, and granulysin+ cells. Results Our data reveal 4 different subgroups of patients associated with distinct signatures of FVIII-specific antibodies. The first subgroup includes 7 subjects who developed FVIII inhibitors by study criteria (B.U. > 0.6 B.U. x 2 measurements from consecutive study days in central laboratory). All 7 subjects had high-risk F8 gene mutations including large deletions (2), intron 22 inversions (4) and duplications (1). Inhibitors in these patients were associated with the development of high-affinity class-switched FVIII-specific antibodies which were detected prior to the first detection of inhibitors. High-affinity IgG1 was generally observed first, followed by high affinity IgG3 and subsequently high-affinity IgG4. Other isotypes and IgG subclasses of anti-FVIII antibodies were only seen occasionally. The second subgroup includes 2 subjects with low titer inhibitors. One subject, who expressed an intron 22 inversion, had a transient low titer FVIII inhibitor (1.4 BU/ml) which was associated with a high-affinity IgG1 antibody only. The other subject, who expressed a frame shift mutation, developed high affinity IgG1 by ED1. This patient had a low titer inhibitor detected (0.8 BU/ml) at ED20 which remained low (0.5 BU/ml) at study end, ED50. No other IgG subclasses were observed in either patient. The third subgroup includes 7 subjects with non-neutralizing antibodies. These subjects expressed intron 22 inversions (3), missense mutations (3) or an intron 1 inversion (1). Six of these patients developed low-affinity IgG1 antibodies which were observed until study end without the appearance of high-affinity antibodies or any other IgG-subclass. No FVIII inhibitors were detected at any time. The remaining subject initially developed low-affinity IgG1 antibodies and subsequently high-affinity IgG1 which remained until study end. No other IgG subclasses and no FVIII inhibitor were detected. The fourth subgroup includes 7 subject who never developed any FVIII-specific antibodies or FVIII inhibitors. These patients expressed missense mutations (3), an intron 22 inversion (1), a duplication (1), a frameshift mutation (1) or a nonsense mutation (1). Relative proportions of circulating FoxP3+ T cells (Tregs), Th17 cells or granulysin+ cells did not correlate with the development of FVIII inhibitors or FVIII-specific antibodies in individual PUPs. Conclusions Data obtained from the HIPS study identify four distinct patient subgroups based on their specific antibody signatures. Most importantly, high affinity class-switched antibodies preceded clinical inhibitor detection, substantiating their potential role as suitable predictive biomarkers for inhibitor development. Disclosures Gangadharan: Shire: Employment. Reipert:Shire: Employment, Equity Ownership. Berg:Research Institute for Applied Bioanalytics and Drug Development, IMC Fachhochschule Krems /: Research Funding. Scheiflinger:Shire: Employment, Equity Ownership. Blatny:Shire, Pfizer, Roche: Consultancy, Speakers Bureau. Fijnvandraat:CSL Behring, Bayer, Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gruppo:Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees. Male:CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biotest: Speakers Bureau; Novo Nordisk: Speakers Bureau; Octapharma: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Speakers Bureau; SOBI: Speakers Bureau. McGuinn:Shire: Research Funding; BioMarin: Consultancy; CSL Behring: Consultancy; Pfizer: Research Funding; Spark: Consultancy, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy. Meeks:HEMA Biologics: Other: Advisory Board; Genentech: Other: Advisory Board; Catalyst Biosciences: Other: Advisory Board; CSL Behring: Other: Advisory Board; Bayer: Other: Advisory Board; Bioverativ: Other: Advisory Board; Shire: Other: Advisory Board; Pfizer: Research Funding. Ragni:MOGAM: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Sangamo: Research Funding; SPARK: Consultancy, Research Funding; Novo Nordisk: Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Research Funding; Alnylam: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Consultancy, Research Funding. Recht:Shire: Research Funding; Biogen: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees. Santagostino:Bayer, Shire, CSL Behring, Pfizer, Novo Nordisk, Grifols, Kedrion, Sobi, Bioverativ, Octapharma, Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shapiro:Bayer Healthcare: Other: International Network of Pediatric Hemophilia; Octapharma: Research Funding; Prometic Life Sciences: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bio Products Laboratory: Consultancy; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sangamo Biosciences: Consultancy; Kedrion Biopharma: Consultancy, Research Funding; Bioverativ, a Sanofi Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; OPKO: Research Funding; BioMarin: Research Funding. Staber:NovoNordisk: Consultancy; Bayer: Honoraria; uniQure: Honoraria. Brown:Shire: Research Funding.
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Daver, Naval G., Harry P. Erba, Nikolaos Papadantonakis, et al. "A Phase I, First-in-Human Study Evaluating the Safety and Preliminary Antileukemia Activity of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, in Patients with Relapsed/Refractory Acute Myeloid Leukemia and Other CD123-Positive Hematologic Malignancies." Blood 132, Supplement 1 (2018): 27. http://dx.doi.org/10.1182/blood-2018-99-112955.
Full textAbstract:
Abstract INTRODUCTION: Overexpression of CD123, the alpha subunit of the IL-3 receptor, in multiple hematological malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN), makes this antigen an attractive target for the development of new therapeutics. IMGN632 is a CD123-targeting antibody-drug conjugate comprising a novel humanized anti-CD123 antibody coupled, via a peptide linker, to a unique DNA-alkylating payload of the recently developed IGN (indolinobenzodiazepine pseudodimer) class of cytotoxic compounds. In preclinical models, IMGN632 exhibited potent antitumor activity with a wide therapeutic index in AML, BPDCN, and ALL, suggesting the potential for robust efficacy along with favorable tolerability in patients with leukemia. We report the initial safety and antileukemia activity findings from the dose-escalation stage of the first-in-human trial of IMGN632. METHODS: The objectives of this ongoing Phase I study (NCT03386513) include determination of the dose-limiting toxicity (DLT), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antileukemia activity of IMGN632. Adult patients with CD123-positive, relapsed or refractory AML or BPDCN are eligible to enroll in the dose-escalation stage. IMGN632 is administered intravenously on Day 1 of a 21-day cycle using a standard 3+3 design. The starting dose of IMGN632 was 0.015 mg/kg, with escalation following a modified Fibonacci schema. Adverse events (AEs) are evaluated by CTCAE v4.03 and tumor responses assessed according to the European LeukemiaNet (ELN) response criteria. RESULTS: At the time of this analysis, a total of 12 patients had received IMGN632 across four dose-escalation cohorts, with dosing successfully escalated from 0.015 mg/kg up to 0.18 mg/kg. The median age of the patients was 66 years (range, 40-80). All patients were diagnosed with AML, including five with relapsed refractory disease and six enrolled at first relapse. Eight patients had received prior intense therapy, including stem cell transplant in two individuals. Seven patients had adverse risk cytogenetics and 50% had secondary AML. No DLTs have been observed at doses up to 0.18 mg/kg (cohort 4) and no discontinuations due to an AE have occurred. The most commonly observed treatment-emergent AEs of any grade were primarily gastrointestinal (decreased appetite, diarrhea, nausea; 25-42%), hematologic (febrile neutropenia; 42%), or vascular (peripheral edema, hypotension, sinus tachycardia; 25-33%). The most frequent Grade 3+ AEs were febrile neutropenia (5 patients; 42%) and lung infection (3 patients; 25%); none of these events were considered related to IMGN632. No grade 3 or higher vascular events were noted. No correlations between the severity, frequency, or nature of reported AEs with increasing dose have been observed. Post-infusion reactions were seen in nine patients (75%). These events typically manifested as mild (grade 1) fever, chills, tachycardia, or nausea/vomiting, occurred less than 24 hours following infusion, and resolved with standard medical care. Steroid premedication has now been implemented at cohort 4. Three deaths occurred, all due to disease progression and unrelated to study drug. In 12 evaluable patients, four (33%) achieved an objective response, including one complete remission (CR) and three complete remissions with incomplete recovery (CRi). Maximal bone marrow blast decreases from baseline seen for patients are presented in Figure 1A. PK analyses showed that systemic IMGN632 exposure and maximum concentrations increased with dose; similarly, PD determinations revealed that the extent and duration of CD123 saturation also increased with dose (Figure 1B). CONCLUSIONS: Objective responses (CR and CRis) were seen in one third of relapsed/refractory AML patients during the initial stages of dose escalation in this first-in-human clinical trial with IMGN632, a novel CD123-targeting ADC. No dose limiting toxicities have been observed, and PK and PD data support continued dose escalation, which is ongoing. Figure 1. A. Maximum percent changes in bone marrow blasts from baseline. Patients who achieved an objective response (CR or CRi) are shown in gray. B. CD123 receptor saturation. Average saturation curves for the first four cohorts are presented. Disclosures Daver: Karyopharm: Research Funding; ARIAD: Research Funding; ImmunoGen: Consultancy; Novartis: Research Funding; Novartis: Consultancy; Otsuka: Consultancy; Karyopharm: Consultancy; Pfizer: Research Funding; Incyte: Research Funding; Kiromic: Research Funding; Pfizer: Consultancy; Sunesis: Research Funding; Daiichi-Sankyo: Research Funding; Alexion: Consultancy; Incyte: Consultancy; Sunesis: Consultancy; BMS: Research Funding. Erba:Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Agios: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Amgen: Research Funding; Astellas: Research Funding; Novartis: Consultancy, Speakers Bureau; Amgen: Research Funding; Immunogen: Consultancy, Research Funding; Amgen: Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda/Millenium: Research Funding; Incyte: Consultancy, Speakers Bureau; Janssen: Research Funding; Seattle Genetics: Consultancy, Research Funding; Pfizer: Consultancy, Other: grant; Celgene: Consultancy, Speakers Bureau; Astellas: Research Funding; Astellas: Research Funding; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: grant; Daiichi Sankyo: Consultancy, Research Funding; Immunogen: Consultancy, Research Funding; Janssen: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Celgene: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Janssen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; MacroGenics: Consultancy; Pfizer: Consultancy, Other: grant; MacroGenics: Consultancy; Juno: Research Funding; Pfizer: Consultancy, Other: grant; Juno: Research Funding; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Celgene: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; MacroGenics: Consultancy; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Juno: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Juno: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau. Papadantonakis:Agios pharmaceuticals: Honoraria, Other: advisory board. DeAngelo:ARIAD: Consultancy, Research Funding; Blueprint Medicines: Honoraria, Research Funding; Takeda: Honoraria; Incyte: Consultancy, Honoraria; BMS: Consultancy; Glycomimetics: Research Funding; Shire: Honoraria; Amgen: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria; Pfizer Inc: Consultancy, Honoraria. Wang:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Jazz: Speakers Bureau; Amgen: Consultancy; Novartis: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Konopleva:Stemline Therapeutics: Research Funding. Sloss:ImmunoGen: Employment. Culm-Merdek:ImmunoGen: Employment.
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Cid, Ana Rosa, Carmen Escuriola, Cedric R. Hermans, et al. "Feiba Global Outcome Study (FEIBA-GO): Long-Term Real World Data on Apcc (FeibaR) in Patients with Inhibitors. First Demographic Data." Blood 128, no. 22 (2016): 5038. http://dx.doi.org/10.1182/blood.v128.22.5038.5038.
Full textAbstract:
Abstract Introduction: Data on APCC´s effectiveness, safety and quality of life are relatively poor because of the rarity of patients with FVIII or FIX inhibitors, the small populations included in clinical trials and the relatively short follow-up available. The FEIBA-GO study was designed to capture long-term outcomes on effectiveness, safety and health-related quality of life (HR-QoL) in subjects receiving APCC in different settings in routine clinical practice. Primary objective is to describe the hemostatic effectiveness of APCC in different settings (prophylaxis and on demand, including patients on immune tolerance induction); most relevant secondary objectives aim at describing joint functionality outcomes, safety, HR-QoL, daily activity level, acute and chronic pain associated with hemophilia, as well as healthcare resources used. Methods: The study is a prospective, non-interventional, multicenter cohort study in patients with hemophilia A or B and high-responding inhibitors treated with APCC. A hundred subjects are targeted for enrollment; treatment regimens are at the discretion of the attending physicians in accordance with routine clinical practice, either on early, secondary or tertiary prophylaxis or on demand, including patients treated with APCC during immune tolerance induction. The observation period per subject will be 4 years. Results: As of June 1, 2016, 40 centres have been qualified in 14 countries and 16 centres have been initiated. 27 patients have been enrolled at 14 open sites in 7 countries. Demographic data are available for the 27 patients enrolled so far and are presented for the first time. All patients have severe hemophilia A: 23 are caucasian, 1 african (3 missing). At the enrolment, 18 of them were on prophylaxis and 6 treated on demand (3 missing). Overall median age is 19 years (min-max: 3-71), 17.5 years in patients on prophylaxis (min-max: 3-71) and 39.5 years in patients on demand (min-max: 22-65). Overall median inhibitor titer at enrolment was 8 BU (min-max: 1-2410), 8 BU for prophylaxis (min-max: 1-92) and 12 BU in patients on demand (min-max: 3-35). Nijmegen modified Bethesda assay was used in 18 centres, while 4 used non-modified Nijmegen Bethesda assay (5 missing). Six subjects (3 on prophylaxis, 2 on demand and 1 unknown) have been reported to have overall 13 target joints. Assessment for acute pain was performed in 12 patients and for chronic pain in 9 patients. Two of 12 patients assessed reported acute pain (both on demand). Two of the 9 patients in whom the assessment was performed reported chronic pain (treatment regimen missing). For one patient, information is not available and for another one it has been reported that pain assessment is not routine examination. Gilbert Score was assessed in 6 patients at screening. Discussion/Conclusion: This study will further enhance the information on long-term effectiveness, HR-QoL and safety of APCC across and beyond Europe in the real world on hemophilia A and B patients with high-responding inhibitors under a variety of prescribing regimens in routine clinical practice. Disclosures Cid: Baxalta Innovations GmbH, now part of Shire: Other: Investigator Clinical Studies. Escuriola:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Biotest: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; NovoNordisk: Consultancy, Honoraria, Research Funding. Hermans:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies. Holme:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies. Negrier:LFB: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; SOBI: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Baxter: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Alnylam: Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; NovoNordisk: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Rangarajan:Baxter: Research Funding; Grifols: Consultancy, Research Funding; Biogen: Consultancy; Pfizer: Research Funding; Baxalta, now part of Shire: Other: Investigator Clinical Studies, Research Funding; Novo Nordisk: Research Funding; Biotest: Research Funding. Rocino:Baxalta, now part of Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy, Honoraria; Kedrion: Consultancy, Honoraria; Sobi: Consultancy, Honoraria. Windyga:Octapharma: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Alexion: Other: Speaker's honorarium; Biogen: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Sanofi: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Aspen: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Nordisk: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Baxalta, now part of Shire: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies, Patents & Royalties, Research Funding, Speakers Bureau. Gringeri:Shire: Employment, Equity Ownership. Crea:Shire: Employment, Equity Ownership.
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Leebeek, Frank W. G., Karina Meijer, Michiel Coppens, et al. "AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B Confirm Stable FIX Expression and Durable Reductions in Bleeding and Factor IX Consumption for up to 5 Years." Blood 136, Supplement 1 (2020): 26. http://dx.doi.org/10.1182/blood-2020-139225.
Full textAbstract:
Background: Gene therapy aims to provide long-term therapeutic benefit from a single administration. AMT-060 is an adeno-associated virus serotype 5 (AAV5) vector with a codon-optimized wildtype human factor IX (FIX) gene and liver-specific promoter. AMT-060 is being evaluated in an ongoing study of 10 participants with severe/moderate-severe hemophilia B (Phase 1/2 study, NCT02396342) over 5 years. Aim: To describe efficacy and safety outcomes from an analysis at up to 5-years post-AMT-060. Methods: Adult males with FIX activity ≤2% and a severe bleeding phenotype received a single intravenous infusion of AMT-060 (5x1012 gc/kg, Cohort 1, n=5) or (2×1013 gc/kg, Cohort 2, n=5). Assessments included FIX activity, FIX replacement use, annualized bleeding rate (ABR), treatment-related adverse events (TRAE), immunological and inflammatory biomarkers up to 5 years (Cohort 1) and 4.5 years (Cohort 2). Results: As of November 2019, for Cohort 1 the mean FIX activity (at 4.0 years) was 5.1% as compared to 4.4% in the first year, 6.8% in the second year, 7.3% in the third year and 7.0% in the fourth year. Mean FIX activity for Cohort 2 was 7.5% as compared to 7.1% in the first year, 8.4% in the second year 7.9% in the third year, and 7.4% in the fourth year. Eight of 9 participants using prophylaxis at baseline were able to discontinue use. During the last 12, and 6 months of observation respectively, the mean annualized bleed rate (ABR) was 3.3. for Cohort 1 and 0.0 for Cohort 2. These represent, respectively, a reduction in mean ABR to the year prior to treatment of 77% and 100% for Cohort 1 and Cohort 2. During this same period the consumption of FIX replacement therapy declined 90% and 100% relative to pre-treatment, respectively for Cohort 1 and Cohort 2. No participants developed FIX inhibitors or signs of sustained AAV5 capsid-specific T-cell activation. As previously reported, TRAE were mainly reported in the first 3.5 months after treatment, including three participants who experienced transient mild elevations in alanine aminotransferase. One additional TRAE (joint swelling post-exercise) was observed during the last 12 months of observation post-treatment. Updated data, up to 5-years of observation, will be presented for the first time. Conclusions: Long-term stable endogenous FIX activity and reductions in ABR and FIX replacement use were sustained over multiple years following a single treatment with AMT-060. There were no additional safety concerns with longer term follow-up. This data supports the ongoing Phase 3 study of the enhanced construct etranacogene dezaparvovec (AMT-061), which encodes the highly active Padua FIX variant. Disclosures Meijer: Bayer: Research Funding; Sanquin: Research Funding; Pfizer: Research Funding; Bayer: Speakers Bureau; Sanquin: Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; BMS: Speakers Bureau; Aspen: Speakers Bureau; Uniqure: Consultancy. Kampmann:Uniqure: Speakers Bureau; Shire Pharmaceuticals: Speakers Bureau. Klamroth:CSL Behring: Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Biotest: Speakers Bureau; Grifols: Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau. Castaman:Novo Nordisk: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Research Funding; Ablynx: Honoraria; Alexion: Honoraria; Bayer: Honoraria; CSL Behring: Honoraria, Research Funding; Kedrion: Speakers Bureau; Sobi: Honoraria, Research Funding, Speakers Bureau; Uniqure: Honoraria, Membership on an entity's Board of Directors or advisory committees; Werfen: Speakers Bureau; Baxalta/Shire: Honoraria. Bönig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Healthineers: Current equity holder in publicly-traded company; Sandor-Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Polyphor: Research Funding; Miltenyi: Honoraria, Research Funding; Erydel: Research Funding; Chugai: Honoraria, Research Funding; Bayer: Research Funding; Terumo BCT: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kiadis: Honoraria; Uniqure: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Stage: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fresenius: Honoraria; medac: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Sawyer:uniQure: Current Employment. Miesbach:UniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BioMarin Pharmaceutical Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: AMT-060 = AAV5 vector gene therapy in subjects with moderate to severe hemophilia B
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Abbott, Brian. "Workplace and employment characteristics of Citizens' Advice Bureau (CAB) clients." Employee Relations 29, no. 3 (2007): 262–79. http://dx.doi.org/10.1108/01425450710741748.
Full textAbstract:
PurposeThere is a paucity of information on the characteristics and reasons for workers contacting the CAB with employment problems. This paper seeks to fill this gap in people's knowledge by providing a detailed profile of the employment and personal characteristics of Citizens' Advice Bureau (CAB) clients.Design/methodology/approachA total of eight bureaux, from contrasting localities in Greater London, participated in the research. The data for this paper are derived predominantly from interviews with CAB clients and reinforced by quantitative data, which were also garnered.FindingsIt is argued that the use of the CAB, for employment advice, is rooted in a structural rather than an attitudinal explanation.Originality/valueThere is a growing recognition within the industrial relations literature of the increasing plurality of sources of representation available to workers. However, very little is known about those employees seeking advice and representation and the types of issues with which they approach bureaux.
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Ruggles, Steven. "Comparability of the Public Use Files of the U.S. Census of Population, 1880–1980." Social Science History 15, no. 1 (1991): 123–58. http://dx.doi.org/10.1017/s0145553200021039.
Full textAbstract:
Most of the information released by the Census Bureau has always consisted of summary population counts cross-tabulated by individual or family characteristics. Although these data form the basic description of the American population, they are not ideal for analytical research. The Census Bureau cannot anticipate all the needs of social scientists, so many topics are inadequately covered in the published census volumes. For historical research, the problem is especially acute, because the published data are fairly sketchy for the period before 1940. Moreover, the classifications employed by the Census Bureau have changed over time, making long-term comparisons difficult or impossible.
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Gonzalez-Lopez, Tomas Jose, Fernando Fernandez-Fuertes, Maria Cristina Pascual Izquierdo, et al. "Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers." Blood 134, Supplement_1 (2019): 2352. http://dx.doi.org/10.1182/blood-2019-129274.
Full textAbstract:
Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.
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Mukherjee, Sudipto, Mehrdad Abedi, Harry P. Erba, et al. "Healthcare Resource Utilization (HCRU) in Patients (pts) with Newly Diagnosed (ND) Acute Myeloid Leukemia (AML) Treated in the Connect® MDS/AML Disease Registry." Blood 132, Supplement 1 (2018): 4736. http://dx.doi.org/10.1182/blood-2018-99-112935.
Full textAbstract:
Abstract Introduction: A number of treatment (Tx) options are available for ND AML pts including high-intensity (HI) chemotherapy ("7+3" regimen) followed by consolidation chemotherapy or allogeneic hematopoietic cell transplantation, low/intermediate-intensity (LI) therapies (low-dose cytarabine or hypomethylating agents), best supportive care (BSC), or no Tx. While data describing HCRU by AML pts informs health systems, clinicians, and pts of the requirements for managing AML pts, HCRU studies in this population are lacking. An analysis of ND AML pts from the Connect® MDS/AML Disease Registry was conducted to examine HCRU in pts receiving different Tx modalities. Methods: The Connect MDS/AML Disease Registry (NCT01688011) is an ongoing, prospective observational cohort study of pts in the USA with ND AML (aged ≥ 55) or myelodysplastic syndromes (aged ≥ 18). All interventions are conducted in accordance with physicians' standard of care. Pt demographics, disease characteristics, and Tx information were collected at screening and every 3 months from AML pts enrolled from December 2013 to March 2018. HCRU was assessed in ND AML pts according to Tx groups defined as HI, LI, BSC, or no Tx initiated ≤ 45 days post-diagnosis. Unplanned hospitalizations related to disease or Tx-related complications were assessed in all pts at 3 and 6 months post-enrollment. Response to Tx was analyzed in pts receiving HI and LI therapy only. Number of transfusion episodes (red blood cell or platelet) was calculated over 6 months post-enrollment, and at each month in pts receiving HI or LI therapy; data for partial months were excluded to accurately assess transfusion episodes/month. Results: A total of 434 AML pts, treated at 20 academic and 85 community/government centers, were included in the analysis. Median age was 70 years (range 55-92), 65% were male, and 83% were white. 95 (21.9%) pts received BSC/no Tx, 153 (35.3%) received LI therapy and 186 (42.9%) received HI therapy. A higher proportion of pts receiving HI therapy had ≥ 1 hospitalization compared with LI and BSC/no Tx groups (59.7% vs 49.0% vs 24.2%; P < 0.05). Mean number of hospitalization days/month in the HI, LI, and BSC/no Tx groups was 6.8 vs 5.7 vs 3.2 days, respectively. During the first 3 months of Tx, pts in the HI group spent a mean of 20.5 days in hospital vs 11.4 days for pts in the LI group, and 9.5 days for pts receiving BSC/no Tx. During the last 3 months of the study period, the number of hospitalization days decreased across all Tx groups to 10.4, 7.0, and 7.7 days, respectively. There were significant differences in mean monthly transfusion burden over the first 6 months of the study for pts in the HI and LI groups (4.9 vs 2.7 transfusion episodes/month; P < 0.01). During month 1 post-enrollment, the mean number of transfusion episodes in the HI group was 8.3 vs 3.4 in those receiving LI therapy (P < 0.01 after adjusting for insurance status). Over the 6-month study period, the transfusion rate decreased in both groups with a mean decrease of 6.3 and 1.8 transfusion episodes from month 1 to month 6 for HI and LI therapy, respectively (P < 0.01). At month 4, the transfusion rate in pts receiving HI therapy fell below that of the LI group (Figure), coinciding with the end or near completion of consolidation chemotherapy in the HI group. In logistic regression analyses, pts receiving HI therapy were significantly more likely to achieve complete remission (CR) vs pts receiving LI therapy, after adjusting for age, comorbidities, and disease risk (odds ratio = 4.2, 95% confidence interval 1.7-9.1; P < 0.01). Results from a sensitivity analysis, which excluded pts who had received a transplant, were consistent with the main analysis. Mortality rates were not significantly different between LI and HI groups at day 30 and day 60 but were at day 180 (P < 0.01; Table). Conclusions: These findings from the Connect MDS/AML Disease Registry highlight the level of HCRU in ND AML pts treated with different intensity therapies. While HCRU, as measured by transfusion burden and unplanned hospitalizations, was highest in the HI group, pts in the HI group were significantly more likely to achieve CR, and had lower mortality rates at a 180-day landmark. Higher HCRU rates during early Tx in the HI group are likely a reflection of cytopenia-related complications due to the highly myelosuppressive nature of HI regimens. Therefore higher HCRU during early therapy in the HI group may be offset by improved pt outcomes. Disclosures Abedi: BMS: Speakers Bureau; CIRM: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Erba:Astellas: Research Funding; Janssen: Research Funding; Janssen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Amgen: Research Funding; Pfizer: Consultancy, Other: grant; Novartis: Consultancy, Speakers Bureau; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas: Research Funding; Janssen: Research Funding; Celgene: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Amgen: Research Funding; Immunogen: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Janssen: Research Funding; Amgen: Research Funding; Jazz: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Astellas: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Pfizer: Consultancy, Other: grant; Daiichi Sankyo: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Pfizer: Consultancy, Other: grant; Takeda/Millenium: Research Funding; MacroGenics: Consultancy; Pfizer: Consultancy, Other: grant; MacroGenics: Consultancy; Juno: Research Funding; Juno: Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Jazz: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Immunogen: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Juno: Research Funding; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Juno: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Agios: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau. Pollyea:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy; Curis: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; Celgene Corporation: Consultancy; Roche/Genentech: Consultancy; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Sandoz: Consultancy; Daiichi Sankyo: Consultancy; Janssen Pharmaceuticals: Consultancy; Orsenix: Consultancy; AbbVie: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celltrion: Consultancy; Aphivena Therapeutics: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Jazz Pharmaceuticals: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Cellectis: Research Funding. Louis:Celgene: Employment; Cellmedica: Patents & Royalties. Flick:Celgene: Employment. Nifenecker:Celgene: Employment. Kiselev:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Cogle:Celgene: Other: Steering Committee Member of Connect MDS/AML Registry.
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Matsuda, Kensuke, Taisuke Jo, Kazuhiro Toyama, Kumi Nakazaki, Hideo Yasunaga, and Mineo Kurokawa. "Early Death in Patients with Disseminated Intravascular Coagulation during Induction Therapy for Acute Promyelocytic Leukemia: A Nationwide Analysis." Blood 136, Supplement 1 (2020): 31. http://dx.doi.org/10.1182/blood-2020-134554.
Full textAbstract:
Background: Real-world data studies showed poorer outcomes in patients with acute promyelocytic leukemia (APL) than randomized controlled trials, because elderly patients were excluded in such trials. Reportedly, the main cause of death was severe bleeding due to disseminated intravascular coagulation (DIC) during induction therapy for APL. The management of DIC was therefore crucially important especially in elderly patients. This study aimed to clarify factors associated with in-hospital death in all patients, and elderly patients with DIC during induction therapy for APL. Study Design and Methods: We retrospectively identified 1,463 patients with newly diagnosed APL who received induction therapy including all-trans retinoic acid (ATRA) between July 2007 and March 2018 from a nationwide inpatient database in Japan. In-hospital death was evaluated with multivariable logistic regression models in all patients, and in ≥60 year-old patients. Anticoagulants included recombinant human soluble thrombomodulin, delteparin (low molecular weight heparin), danaparoid sodium, gabexate mesilate, and nafamostat mesilate which were administered within three days from admission. Patients who died within three days from the admission were excluded from the study to avoid immortal time bias. Results: We identified a total of 1,138 (78%) patients who developed DIC. We excluded 23 patients who died within three days from the admission. The remaining 1,115 patients were analyzed. During hospitalization, 172 (15%) patients died at a median of 13 days (interquartile range: 7-30). Compared with younger patients (20 to 39 years old), elderly patients were significantly associated with higher in-hospital mortality (60 to 79 years old: odds ratio 5.58 [95% confidence interval 3.05-10.22], 80 years or older: 13.51 [6.07-30.08]). Patients who received ATRA monotherapy had significantly higher incidence of in-hospital death (2.48 [1.54-4.01]). Delayed initiation of ATRA was significantly associated with higher mortality (1.60 [1.11-2.30]). A total of 699 patients (63%) received anticoagulant therapies, but none of these were significantly associated with lower mortality. Use of multiple anticoagulants was significantly associated with higher in-hospital mortality (2.47 [1.16-5.26]). Subgroup analyses in patients ≥60 years old were then conducted. During hospitalization, 122 of 416 (29%) patients died at a median of 13 days (interquartile range: 7-29). Both late initiation of conventional chemotherapy and no conventional chemotherapy were significantly associated with higher in-hospital mortality (1.88 [1.01-3.49], 3.25 [1.74-6.06], respectively). Use of recombinant human soluble thrombomodulin and use of multiple anticoagulants were significantly associated with higher mortality (1.91 [1.09-3.35], 2.64 [1.01-6.90], respectively). Conclusions: Elderly patients who developed DIC during induction therapy for APL were significantly associated with higher in-hospital mortality. Immediate initiation of ATRA and early initiation of conventional chemotherapy may have contributed to preferable outcomes. Disclosures Matsuda: Kyowa Kirin: Speakers Bureau. Jo:Tsumura: Other: Belongs to joint program with Tsumura, Research Funding. Toyama:Bristol-Myers Squibb: Speakers Bureau; Eisai: Speakers Bureau; Kyowa Kirin: Speakers Bureau; Celgene: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Nippon Shinyaku: Speakers Bureau; Chugai Pharmaceutical,: Speakers Bureau; Ono Pharmaceutical: Speakers Bureau; Otsuka Pharmaceutical: Speakers Bureau; Takeda Pharmaceutical: Speakers Bureau. Kurokawa:Ono: Research Funding, Speakers Bureau; Jansen Pharmaceutical: Speakers Bureau; Teijin: Research Funding; Eisai: Research Funding, Speakers Bureau; Shire Plc: Speakers Bureau; Nippon Shinyaku: Research Funding, Speakers Bureau; MSD: Consultancy, Research Funding, Speakers Bureau; Chugai: Consultancy, Research Funding, Speakers Bureau; Sanwa-Kagaku: Consultancy; Pfizer: Research Funding; Otsuka: Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Bioverativ Japan: Consultancy; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma: Research Funding, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau.
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Gerds, Aaron T., Alessandro M. Vannucchi, Francesco Passamonti, et al. "Duration of Response to Luspatercept in Patients (Pts) Requiring Red Blood Cell (RBC) Transfusions with Myelofibrosis (MF) - Updated Data from the Phase 2 ACE-536-MF-001 Study." Blood 136, Supplement 1 (2020): 47–48. http://dx.doi.org/10.1182/blood-2020-137265.
Full textAbstract:
Introduction: MF is a clonal stem cell disorder characterized by progressive bone marrow failure, extramedullary hematopoiesis, and debilitating constitutional symptoms. Approximately 60% of pts develop anemia within a year of diagnosis; pts who are transfusion dependent have worse survival and quality-of-life outcomes (Tefferi A, et al. Mayo Clin Proc 2012;87:25-33). Treatment for MF-associated anemia remains critically unaddressed, with no approved therapies available. Luspatercept is a first-in-class erythroid maturation agent that has been shown to increase hemoglobin and reduce transfusion burden in pts with myelodysplastic syndromes (Fenaux P, et al. N Engl J Med 2020;382:140-51) and β-thalassemia (Cappellini MD, et al. N Engl J Med 2020;382:1219-31). Pts have also achieved multiple response episodes with luspatercept (Fenaux P, et al. Blood 2019;134:841). We previously reported findings from the ongoing open-label, phase 2 ACE-536-MF-001 trial evaluating luspatercept in pts with MF-associated anemia (Gerds AT, et al. Blood 2019;134:557). Here we report updated study results, focusing on response in pts requiring RBC transfusions. Methods: 79 pts with MF and anemia were enrolled (Figure). Of these, 43 were requiring RBC transfusions, defined as 6-12 U/84 d prior to treatment, or 4-12 U/84 d for the 3 expansion cohort pts. Pts in Cohort 3B received a stable ruxolitinib (RUX) dose for ≥ 16 wks (40 wks for expansion cohort pts), whereas Cohort 2 pts did not (Figure). Pts in Cohort 3B received a median RUX dose of 20 mg/d (range 5-40) for a median of 73 wks (range 29-359) prior to treatment. Pts received luspatercept every 21 d at a starting dose of 1.0 mg/kg (1.33 mg/kg for 3 expansion cohort pts in Cohort 3B), with doses escalating up to 1.75 mg/kg; 81% and 50% of pts in Cohorts 2 and 3B escalated to 1.75 mg/kg. Primary endpoint for pts receiving transfusions was RBC transfusion-independence (RBC-TI) for ≥ 12 consecutive wks within the first 24 wks on study. However, as responses were observed that did not fall within the 24-wk response window, additional assessments were conducted for the entire treatment duration for RBC-TI and ≥ 50% decrease in RBC transfusions (minimum 4 RBC U decrease) from baseline. Intent-to-treat data were analyzed as of March 29, 2020. Results: Pts in Cohorts 2 and 3B received a median of 8 cycles of luspatercept (range 1-39), for a median (mean) duration of 24 (31) and 23 (39) wks, respectively. Pts in Cohorts 2 and 3B received a median of 2.7 RBC U/28 d (range 1-5) and 2.7 RBC U/28 d (range 2-4), respectively. For the primary endpoint, 2/21 (10%) and 6/22 (27%) pts receiving transfusions in Cohorts 2 and 3B achieved RBC-TI over any consecutive 12 wks during the first 24 wks. Median time to start of first RBC-TI response period in Cohorts 2 and 3B was 1.5 days and 37 days; median duration of response was 49 wks (range 16-82) and 42 wks (range 12-111), respectively. When assessing the entire treatment period, 4/21 (19%) and 8/22 (36%) pts in Cohorts 2 and 3B achieved RBC-TI ≥ 12 wks, respectively. 25% of the RBC-TI responders in both cohorts experienced 2 separate episodes of RBC-TI ≥ 12 wks. Median cumulative duration of all individual ≥ 12-wk response episodes of RBC-TI was 59 wks (range 24-82) in Cohort 2 and 55 wks (range 12-116) in Cohort 3B. 8/21 (38%) and 10/22 (46%) pts in Cohorts 2 and 3B achieved a ≥ 50% reduction in RBC transfusion burden (minimum ≥ 4 U reduction) over 12 wks; of these, 38% and 20% of responders in Cohorts 2 and 3B experienced 2 separate ≥ 12-wk response episodes, and 1 pt (13%) in Cohort 2 experienced 3 separate responses. 4/15 (27%) and 8/14 (57%) pts in Cohorts 2 and 3B who reached 24 wks of treatment achieved clinical benefit and therefore continued luspatercept on an ongoing basis. Safety is reported for all 79 pts on study. 5 (6%) pts had grade 3-4 treatment-related adverse events (AEs); these AEs were diarrhea (n = 2), dehydration (n = 1), and hypertension (n = 3). There were no treatment-related deaths. Treatment-related AEs (any grade) occurring in ≥ 5% of pts were hypertension (13%), bone pain (9%), and diarrhea (5%). 8 (10%) pts had ≥ 1 AE leading to discontinuation. 16 (20%) pts remain on treatment. Conclusions: These longer-term findings suggest durable activity of luspatercept in pts with MF-associated anemia. In addition, a quarter of pts receiving transfusions achieved more than one ≥ 12-wk episode of RBC-TI response with luspatercept. The incidence of grade 3-4 AEs with luspatercept was low. Disclosures Gerds: Roche/Genentech: Research Funding; Celgene: Consultancy, Research Funding; Sierra Oncology: Research Funding; AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding; Pfizer: Research Funding; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy, Research Funding; Gilead Sciences: Research Funding; Imago Biosciences: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blueprint: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees. Passamonti:Novartis: Speakers Bureau; BMS: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support. Kremyanskaya:Constellation Pharmaceuticals: Research Funding; Incyte Corporation: Research Funding; Bristol Myers Squibb: Research Funding; Protagonist Therapeutics: Consultancy, Research Funding; Astex Pharmaceuticals: Research Funding. Gotlib:CTI Biopharma: Research Funding; Kartos: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; BMS: Research Funding. McCaul:BMS: Speakers Bureau; Seattle Genetics: Speakers Bureau; Karyopharm: Speakers Bureau; Incyte: Speakers Bureau. Ribrag:argenX: Research Funding; pharmamar: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; servier: Consultancy; nanostring: Honoraria, Membership on an entity's Board of Directors or advisory committees; gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; AZD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other; Infinity: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; gustave roussy comprehensive cancer center: Current Employment; EPZ: Honoraria, Membership on an entity's Board of Directors or advisory committees; epizyme (EPZ): Research Funding. Mead:Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; Celgene/BMS: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding; Abbvie: Consultancy; CTI: Consultancy; Gilead: Consultancy. Harrison:Roche: Honoraria; Gilead Sciences: Honoraria, Speakers Bureau; Incyte Corporation: Speakers Bureau; Janssen: Speakers Bureau; CTI Biopharma Corp: Honoraria, Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; AOP Orphan Pharmaceuticals: Honoraria; Promedior: Honoraria. Mesa:Sierra Oncology: Consultancy; LaJolla Pharmaceutical Company: Consultancy; Novartis: Consultancy; Incyte: Research Funding; CTI BioPharma: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; Promedior: Research Funding; Bristol Myers Squibb: Research Funding; Samus Therapeutics: Research Funding. Kiladjian:AbbVie: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Barosi:Bristol Myers Squibb: Consultancy. Gerike:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Shetty:BMS: Current Employment, Current equity holder in publicly-traded company. Pariseau:Bristol Myers Squibb: Current Employment. Miranda:Bristol Myers Squibb: Current Employment. Schwickart:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Giuseppi:BMS: Current Employment, Current equity holder in publicly-traded company. Zhang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Backstrom:Acceleron Pharma: Current Employment, Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company. Verstovsek:AstraZeneca: Research Funding; Roche: Research Funding; CTI Biopharma Corp: Research Funding; Genentech: Research Funding; Incyte Corporation: Consultancy, Research Funding; NS Pharma: Research Funding; Novartis: Consultancy, Research Funding; PharmaEssentia: Research Funding; ItalPharma: Research Funding; Sierra Oncology: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Protagonist Therapeutics: Research Funding.
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Zinzani, Pier Luigi, Vladimir Melnichenko, Krimo Bouabdallah, et al. "Pembrolizumab Monotherapy in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL): 3-Year Follow-up of the Keynote-170 Study." Blood 136, Supplement 1 (2020): 42–43. http://dx.doi.org/10.1182/blood-2020-137080.
Full textAbstract:
Introduction: No standard of care exists for patients (pts) with relapsed or refractory primary mediastinal B-cell lymphoma (rrPMBCL). As such, pts typically receive therapies recommended for diffuse large B-cell lymphoma, with poor prognosis. Similar to classical Hodgkin lymphoma, rrPMBCL tumors often overexpress the programmed death 1 (PD-1) ligands, PD-L1 and PD-L2. Data from the first full analysis of the phase 2 KEYNOTE (KN)-170 (NCT02576990) study showed that pembrolizumab provided effective and durable antitumor activity with a manageable safety profile in patients with rrPMBCL. These data led to the FDA approval of pembrolizumab for pts with rrPMBCL after ≥2 prior therapies. In this aggressive malignancy with few salvage options, duration of remission with PD-1 blockade remains a critical question. Here we present data from KN170 with an additional 24 months of follow-up in patients with rrPMBCL. Methods: Pts with rrPMBCL who had relapsed after or were ineligible for autologous stem cell transplant with ≥2 lines of prior therapy were enrolled in KN170 to receive 200 mg pembrolizumab IV Q3W until disease progression or toxicity, for up to 2 years. Tumor response was assessed Q12W with PET/CT scans by IWG 2007 criteria. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included response by Lugano 2014 criteria. The data cutoff date for this analysis was May 7, 2020. Results: At the data cutoff date, among all treated pts (N=53), 13 had completed 2 years of treatment and 40 had discontinued largely due to progression (n=30). The ORR was 45% (24/53; 95% CI 32-60) with a CR rate of 19% (10/53; 13/53 [25%] by Lugano criteria). No patient who achieved CR by BICR had received consolidation therapy or had progressed at data cutoff. After a median study follow-up of 43.1 months (range, 35.6-50.7) the median DOR was not reached (range, 1.1+ to 46.9+ mo); 76% of pts had a response duration ≥36 mo. Median PFS was 5.5 mo (95% CI, 2.7-15.1), with 36-mo PFS rate of 34%. The median OS was 22.3 mo (95% CI, 7.3 to not reached) with 36-mo OS rate of 45%. At data cutoff, 50 (94%) pts had at least one adverse event (AE), with 30 (57%) having a treatment-related AE. The most common treatment-related AEs were neutropenia (19%), asthenia (9%), hypothyroidism (8%), fatigue (6%), and pyrexia (6%). Grade ≥3 treatment-related AEs occurred in 12 (23%) pts. Six (11%) pts had an immune-mediated AE. There were no treatment-related grade 5 events. Conclusion: Results from the longer-term follow-up of KN170, the largest prospective clinical trial in rrPMBCL, shows that pembrolizumab provides robust and durable antitumor activity with a manageable safety profile in patients with rrPMBCL. Disclosures Zinzani: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bouabdallah:Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Walewski:Roche: Consultancy, Honoraria, Other: travel expenses, Research Funding; GSK/Novartis: Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy. Caballero:Gilead: Other: travel; Roche: Other: travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: travel; BMS: Other: travel. Christian:Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Özcan:Takeda: Honoraria, Other: travel, Research Funding; Roche: Other: travel, Research Funding; Bayer: Research Funding; Abbvie: Other: travel, Research Funding; Archigen: Research Funding; Celgene: Research Funding; MSD: Research Funding; Novartis: Research Funding; Amgen: Honoraria, Other: travel; BMS: Other; Jazz: Other; Sanofi: Other; Abdi Ibrahim: Other; Janssen: Other: travel, Research Funding. Salles:Bristol Myers Squibb: Consultancy, Other; Takeda: Consultancy, Honoraria, Other; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Debiopharm: Consultancy; Kite: Consultancy, Honoraria, Other; MorphoSys: Consultancy, Honoraria, Other; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Novartis: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Epizyme: Consultancy; Karyopharm: Consultancy; Autolus: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Genmab: Consultancy. Shipp:Celgene: Honoraria; Ono Pharmaceutical: Honoraria; Bayer: Honoraria; Bristol Myers Squibb: Consultancy, Research Funding; Merck: Research Funding. Thompson:Merck Sharp & Dohme Corp.: Current Employment. Orlowski:Merck Sharp & Dohme Corp.: Current Employment. Marinello:Merck & Co., Inc., Kenilworth, NJ, USA: Other: Stock ownership; Merck & Co., Inc.: Other: Travel, accommodations, expenses; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Current Employment. Armand:Pfizer: Consultancy; Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy, Research Funding; Affimed: Consultancy, Research Funding; Sigma Tau: Research Funding; Celgene: Consultancy; IGM: Research Funding; Otsuka: Research Funding; Tensha: Research Funding; Genentech: Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Roche: Research Funding.
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Cortes, Jorge E., Daniel J. DeAngelo, Harry P. Erba, et al. "Maturing Clinical Profile of IMGN779, a Next-Generation CD33-Targeting Antibody-Drug Conjugate, in Patients with Relapsed or Refractory Acute Myeloid Leukemia." Blood 132, Supplement 1 (2018): 26. http://dx.doi.org/10.1182/blood-2018-99-112891.
Full textAbstract:
Abstract INTRODUCTION: The myeloid differentiation antigen CD33 is an established therapeutic target in acute myeloid leukemia (AML). In addition to its broad expression on leukemic cells of most patients with AML, the endocytic properties of the receptor make it well suited for antibody-drug conjugate (ADC)-based strategies. IMGN779 is a next-generation anti-CD33 ADC with a novel DNA-alkylating IGN (indolinobenzodiazepine pseudodimer) payload and a cleavable s-SPDB linker, which entered clinical evaluation based on potent preclinical antitumor activity and superior tolerability compared with DNA-crosslinking payloads. We report safety and antileukemia activity findings from the ongoing dose escalation study of IMGN779 in patients with relapsed or refractory AML. METHODS: The objectives of this Phase I study (NCT02674763) include determination of the dose-limiting toxicity (DLT), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antileukemia activity of IMGN779. Adult patients with relapsed or refractory CD33+ AML (defined as ≥ 20% of blasts expressing CD33 by flow cytometry) are eligible. IMGN779 is administered intravenously and dose escalation follows a standard 3+3 design. Two schedules have been evaluated to date: once every 2 weeks (Q2W; i.e. Days 1 and 15 of a 28-day cycle) and once weekly (QW; Days 1, 8, 15, and 22 of a 28-day cycle). RESULTS: Fifty patients, median age 68 years (range: 27-84), have received IMGN779, with 36 and 14 patients treated on the Q2W and QW schedules, respectively. Sixteen patients (32%) had primary refractory AML, with 39 (78%) having received prior intense frontline therapy, including stem cell transplant in nine (18%) patients. Dosing using the Q2W schedule commenced at 0.02 mg/kg and has been escalated to 1.5 mg/kg (cohort 11). QW dosing was initiated at 0.39 mg/kg and escalation has proceeded to 0.7 mg/kg (cohort 3). All patients received premedication with steroids. No DLTs have been observed on either schedule. The most commonly observed treatment-emergent AEs seen across both cohorts combined (>20% of patients) were febrile neutropenia, epistaxis, nausea, diarrhea, fatigue, abdominal pain, and hypokalemia. The most frequent Grade 3+ adverse events (AEs) were febrile neutropenia (40%), bacteremia (22%), pneumonia (20%), and anemia (16%). Three patients dosed on the QW schedule discontinued due to an AE. These involved individual cases of grade 3 diverticulitis, grade 4 large intestinal perforation, and grade 4 septic shock; none were considered related to study drug. With a median of 3.5 doses (range: 1-34) administered per patient, there has been no evidence of cumulative toxicity, nor have any correlations been observed between increasing dose and AE frequency, nature, or severity. There have been no study drug-related deaths. For both schedules, dose-dependent increases in Cmax and AUC with prolonged exposure have been observed. A slower elimination phase was observed with higher IMGN779 doses (>0.39 mg/kg) consistent with non-linear pharmacokinetics. CD33 saturation is prolonged in a dose dependent manner and weekly dosing maintains CD33 receptor saturation. Overall, 19 of 24 patients with measurable circulating blasts (79%) showed decreases in blast numbers in the first week of therapy. Figure 1 shows the maximal changes in bone marrow blasts from baseline for all evaluable patients treated at 0.39 mg/kg or above across both dosing schedules. In total, 11/27 patients (41%) who received IMGN779 had a >30% reduction in bone marrow blasts, which included 6/17 (35%) patients in Q2W cohorts 6-11 (0.39-1.5 mg/kg) and 5/10 patients (50%) in QW cohorts 1-2 (0.39-0.54 mg/kg). CONCLUSIONS: IMGN779 continues to display manageable tolerability and antileukemia activity in patients with relapsed or refractory AML, characterized by an adverse event profile that is consistent with the underlying disease and/or comorbidity. PK exposures and PD CD33 saturation continue to increase with dose and support further escalation of both Q2W and QW dosing schedules, which is ongoing. Figure 1. Maximum percent changes in bone marrow blasts from baseline. Patients who received IMGN779 on the QW schedule are shaded black; those on the Q2W schedule are shaded gray. Disclosures Cortes: Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding. DeAngelo:Amgen: Consultancy; Takeda: Honoraria; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria; Blueprint Medicines: Honoraria, Research Funding; Glycomimetics: Research Funding; Pfizer Inc: Consultancy, Honoraria; Shire: Honoraria; Incyte: Consultancy, Honoraria; ARIAD: Consultancy, Research Funding; BMS: Consultancy. Erba:Janssen: Research Funding; Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Janssen: Research Funding; Immunogen: Consultancy, Research Funding; Amgen: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: grant; Immunogen: Consultancy, Research Funding; Astellas: Research Funding; Takeda/Millenium: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Novartis: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Pfizer: Consultancy, Other: grant; Celgene: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Amgen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Daiichi Sankyo: Consultancy, Research Funding; Astellas: Research Funding; Takeda/Millenium: Research Funding; Astellas: Research Funding; Seattle Genetics: Consultancy, Research Funding; Amgen: Research Funding; Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Juno: Research Funding; Pfizer: Consultancy, Other: grant; Juno: Research Funding; Pfizer: Consultancy, Other: grant; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Jazz: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Celgene: Consultancy, Speakers Bureau; Juno: Research Funding; Immunogen: Consultancy, Research Funding; Juno: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Celgene: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Agios: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau. Traer:ImmunoGen: Consultancy; Tolero: Consultancy; Notable Labs: Equity Ownership. Papadantonakis:Agios pharmaceuticals: Honoraria, Other: advisory board. Blum:Forma: Research Funding; Pfizer: Consultancy; Astellas: Consultancy; Xencor: Research Funding; Boehringer Ingelheim: Research Funding; Tolero: Research Funding. Sloss:ImmunoGen: Employment. Culm-Merdek:ImmunoGen: Employment. Wang:Novartis: Speakers Bureau; Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Jazz: Speakers Bureau.
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Liebers, Nora, Johannes Duell, Daniel Nörenberg, et al. "Polatuzumab Vedotin in Relapsed and Refractory (r/r) Large B-Cell Lymphoma (LBCL): Real-World Data of the German National Compassionate Use Program (CUP)." Blood 136, Supplement 1 (2020): 11–13. http://dx.doi.org/10.1182/blood-2020-136539.
Full textAbstract:
Introduction The antibody-drug conjugate polatuzumab vedotin (Pola) has recently been approved in combination with bendamustine and rituximab (Pola-BR) for patients with r/r diffuse LBCL (DLBCL). Methods To characterize the efficacy of Pola-BR in a real-world setting, we retrospectively analyzed data from 97 patients with r/r LBCL who were treated with Pola in 24 German centers within the national CUP. Clinical baseline and follow-up (FU) data were collected by chart review and summarized descriptively. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. Fisher's exact test was used to compare categorical factors between groups of patients. Results 97 patients with LBCL (DLBCL n=90, High-grade B-cell lymphoma n=6, Primary mediastinal B-cell lymphoma n=1) were included as of July 22nd, 2020. 49 patients were treated with Pola as bridging concept to immunotherapies (bridging cohort: chimeric antigen receptor T-cells (CART) n=39, allogeneic stem cell transplantation (alloSCT) n=9, bispecific antibodies n=1), and 48 patients were treated with Pola in palliative intention (palliative cohort). Within the bridging cohort the median age was 61 years (range: 22-82). Patients were heavily pretreated with a median of 3 treatment lines (range: 2-6). 84% (41/49 patients) had been refractory to their last treatment line, and 31% had failed an autologous stem cell transplantation. Notably, 14% and 10% of patients had failed prior CART and alloSCT, respectively, and were planned for the alternate cellular immunotherapy. Based on an individual decision, patients were treated with Pola-Rituximab (Pola-R, n=20), Pola-chemotherapy (Pola-chemo, BR n=25; R-CHP n=1) or Pola-monotherapy (Pola-mono, n=3). With a median of 2 Pola cycles (range 1-6), overall response rate (ORR) of all evaluable patients was 33% (15/46 patients) including patients with complete response (CR n=1), partial response (PR n=9) and clinical response (n=5). Although not significant, ORR tended to be better in patients treated with Pola-chemo versus Pola-R/Pola-mono (ORR: 42% versus 20%, Fishers test p=0.1). 11 of these 15 responders (24% of the entire bridging cohort) proceeded to CART or alloSCT, while 4 responders (8% of entire bridging cohort) experienced fast progression after their initial response and were referred to best supportive care. 15 of 31 non-responders (33% of entire bridging cohort) underwent immunotherapy with either stable disease (n=6), mixed response (n=2), or progression on Pola (n=7). The remaining 16 patients (35% of entire bridging cohort) were all refractory to Pola and either received alternative salvage treatments which enabled 8 further patients to proceed to the intended immunotherapy, or best supportive care. Taking the effects of CART or alloSCT into account, median OS from initiation of Pola treatment was 8.2 months (median FU 7.2 months, Fig. 1A). The palliative cohort tended to be older than the bridging cohort with a median age of 73.5 years (range: 37-86, p&lt;0.001). Patients were pretreated with a median of 3 treatment lines (range: 2-8), and 85% (41/48 patients) had been refractory to their last treatment line. Patients in the palliative cohort were treated with a median of 4 Pola cycles (range: 1-9). 65% received Pola-chemo (BR, n=30; R-Gemcitabine, n=1) and 35% Pola-R. The CR rate and ORR was 19% (9/48) and 56% (27/48), respectively. The 6-month PFS and OS from initiation of Pola was 36% and 51%, respectively (median FU of 9.7 months, Fig. 1B). Again, ORR and OS tended to be better in patients treated with Pola-chemo versus Pola-R (ORR: 61% versus 47%, Fishers test p=0.4; median OS 7.2 versus 4 months, HR 0.8, 95%CI 0.4-1.9, p=0.7). In univariate analysis, failure to respond to the last treatment line predicted inferior PFS (HR 2.4, 95%CI 1.2-5.0 p=0.02) and OS (HR 2.5, 95%CI 1.2-5.4 p=0.02). Patients with more than two prior treatment lines in total tended to have a shorter PFS (HR 2.0, 95% CI 0.9-4.5, p=0.1) and OS (HR 1.8, 95% CI 0.8-4.0, p=0.2), although significance was not reached. Conclusion Pola permits effective bridging to CART and alloSCT in r/r LBCL. In the palliative setting, Pola represents an effective salvage option for patients with transplantation-ineligible r/r LBCL. Compared to the approval study, the inferior outcome of the patients of this real-world analysis might be explained by their more advanced disease course. Disclosures Duell: Morphosys: Research Funding. Kerkhoff:BMS: Honoraria. Leng:Roche: Other: lecture fee; Celgene: Other: traveling expenses and congress attendance fee. Holtick:Miltenyi Biotec B.V. & Co. KG: Honoraria. Mayer:Amgen: Honoraria, Other: travel grants; Abbvie: Other: travel grants; Novartis: Honoraria; Roche: Honoraria. Hüttmann:Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Other: Travel expenses; Seattle Genetics: Research Funding; University Hospital Essen, University of Duisburg-Essen, Essen, Germany: Current Employment; Lead Discovery Center GmbH: Consultancy. Brunnberg:Gilead: Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants; MSD: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Amgen: Other: Travel grants. Bullinger:Menarini: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Hess:Roche: Research Funding; Celgene: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genmab: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; EUSA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mueller-Tidow:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Deutsche Krebshilfe: Research Funding; BMBF: Research Funding; Wilhelm-Sander-Stiftung: Research Funding; Jose-Carreras-Siftung: Research Funding; Bayer AG: Research Funding; Daiichi Sankyo: Research Funding; BiolineRx: Research Funding; Janssen-Cilag Gmbh: Membership on an entity's Board of Directors or advisory committees; Deutsche Forschungsgemeinschaft: Research Funding. Lenz:Verastem: Research Funding; AQUINOX: Research Funding; BMS: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Agios: Research Funding; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy; Morphosys: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Dreger:Roche: Consultancy, Speakers Bureau; Neovii: Research Funding; AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy; Gilead: Consultancy, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding, Speakers Bureau. Dietrich:Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees.
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ROY, Lydia, Jean-Claude Chomel, Joelle Guilhot, et al. "Combination of Dasatinib and Peg-Interferon Alpha 2b in Chronic Phase Chronic Myeloid Leukemia (CP-CML) First Line: Preliminary Results of a Phase II Trial, from the French Intergroup of CML (Fi-LMC)." Blood 126, no. 23 (2015): 134. http://dx.doi.org/10.1182/blood.v126.23.134.134.
Full textAbstract:
Abstract Background: Combination of Pegylated-Interferon alpha (Peg-IFNa) 2a and imatinib (IM) has been reported to significantly induce higher rates of molecular responses (including undetectable BCR-ABL transcript) over IM alone, as frontline therapy for CP-CML patients (pts) in a randomized phase 3 trial (SPIRIT, Preudhomme et al, NEJM 2010). Second generation TKIs such as dasatinib (DASISION, Kantarjian et al, NEJM 2010) enhance the speed and depth of molecular response (MR) in comparison to IM. Phase II trial using nilotinib and PegIFNa2a has recently reported high rates of deep molecular response (MR4.5) within 24 months (Nicolini FE et al, Lancet Haematology 2015). Aims: To determine the efficacy and safety of the combination of dasatinib and Peg-IFNa2b in CP-CML frontline. (EUDRACT Number: 2012-003389-42, Dasa-PegIFN trial). Methods: Newly diagnosed Ph+ CP-CML pts less than 65-year-old started dasatinib 100 mg/day. At 3 months, they were assigned to receive Peg-IFNa2b associated to dasatinib when platelets (plt) > 100 X 109/L, Neutrophils (ANC) > 1.5 X 109/L) and lymphocytes < 4.0 X 109/L counts were achieved. Otherwise, dasatinib was continued alone in the study according to the current international ELN guidelines. The maximum duration of the combination dasatinib and Peg-IFNa2b is 21 months. The primary endpoint is the cumulative rate of Molecular Response 4.5log (MR4.5 defined as BCR-ABL1/ABL1IS≤0.0032%) at 12 months. Molecular analyses were centralized and expressed according to the international scale (IS). Secondary endpoints included efficacy (cytogenetic and molecular responses at several time-points) and safety endpoints. Preliminary results are reported here. Results: 81 pts were enrolled between October 2013 and July 2014. All pts will have completed the 12 months follow-up time-point in August 2015. 79/81pts were included in the analysis (1 pt died of a CML-related haemorrhage before receiving dasatinib, 1 screening failure (masked Ph)). Median age was 48 (20-65) years. 54% of pts were male. Sokal scores were low, intermediate and high in 51%, 32% and 17% of pts respectively. After the first 3 months of therapy (M3), sixty-one patients (77%) started Peg-IFNa2b at the dose of 30 microg/week in association with dasatinib. For these pts after M3, reported hematologic adverse events (AE) were neutropenia (G3/4 n=11; G1/2 n=17), thrombocytopenia (G3/4 n=0; G1/2 n=7), anemia (G3/4 n=0; G1/2 n=7). Extra-hematologic AE were essentially of low grade (overall, G3/4 n=3; G1/2 n=113). According to NCI CTCAE V4.0, most frequent AE were infections (16%), general symptoms (15%), skin lesions (10%), hepato-biliary abnormalities (7.7%), nervous system/headache (7.7%) musculoskeletal pain (7%), psychiatric (7%), GI (6%) disorders. Eight serious AE (SAE) were reported after Peg-IFNa2b initiation: G4 neutropenia n=2, dysthyroitidis n=1, dyspnea n=1, pleural effusion n=1, lymphoid hyperplasia n=1, hemorrhoids n=1, rectal fistula (SUSAR) n=1. Efficacy was analysed according to the intention-to-treat principle (ITT), and considering missing data as no response to avoid inflated results. Overall at M3, 85% of pts had a BCR-ABL1/ABL1 ratio ≤10%. For eligible patients who received combined therapy (n=61), rates of MMR were 16%, 51%, 70%, and 70% (pending n=5) at M3, M6, M9 and M12, including MR4.5 rates 10%, 20%, 30% at M6, M9 and M12 respectively. Eighteen pts (22.7%) were not eligible to receive Peg-IFNa2b. Reasons, according to protocol criteria, were ANC <1.5 X 109/L (n=10), plt <100.0 X 109/L (n=5), lymphocytes >4.0 X 109/L (n=1), absence of complete hematologic response (n=1), non compliance (n=1). Rates of MMR for these pts were 27% at M6, 50 % at M9 (missing n=2), pending data for n=6 at M12. Conclusion: Peg-IFNa2b combined to dasatinib therapy in first line CP-CML induces a high rate of deep molecular response (ie MR4.5) during the first year of therapy. Despite few pending data, results at 12 months are already in line with previous data combining Peg-IFNa and TKI, expecting a potential for an increased rate in therapy cessation attempt. Preliminary data of this phase II trial indicate a manageable toxicity profile for this combination, despite an increased rate of neutropenia. Updated analyses (ITT and per protocol) will be presented for all the pts with at least 12 months follow-up. Disclosures ROY: BMS: Other: CongressTravels/Accomodations, Research Funding, Speakers Bureau; Novartis: Other: Congress Travels/Accomodations, Research Funding, Speakers Bureau; Merck: Other: Peg-Interferon provided in the trial. Guerci-Bresler:Novartis: Speakers Bureau; BMS: Speakers Bureau; ARIAD: Speakers Bureau; PFIZER: Speakers Bureau. Giraudier:BMS: Speakers Bureau; Novartis: Other: Congress Travel/Accomodation, Speakers Bureau. Johnson-Ansah:Hybrigenics SA: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau. Amé:Novartis: Speakers Bureau; BMS: Speakers Bureau. Etienne:BMS: Consultancy, Honoraria, Speakers Bureau; ARIAD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau. Nicolini:BMS: Other: Travel/Accommodations/Expenses; Novartis: Other: Travel, Accommodations, Expenses; ARIAD: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting or Advisory Role, Speakers Bureau; Novartis: Honoraria, Other: Consulting & Advisory Role, Research Funding, Speakers Bureau. Rea:Novartis: Honoraria; BMS: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Cony-Makhoul:Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Ianotto:Novartis: Other: Congress Travel/ Accomodations. Legros:ARIAD: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau. Coiteux:BMS: Speakers Bureau. Hermet:BMS: Speakers Bureau; Novartis: Speakers Bureau. Mahon:BMS: Speakers Bureau; Novartis: Speakers Bureau. Rousselot:ARIAD: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Speakers Bureau.
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Advani, Anjali S., Anna Moseley, Kristen Marie O'Dwyer, et al. "Results of SWOG 1318: A Phase 2 Trial of Blinatumomab Followed By Pomp (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) Maintenance in Elderly Patients with Newly Diagnosed Philadelphia Chromosome Negative B-Cell Acute Lymphoblastic Leukemia." Blood 132, Supplement 1 (2018): 33. http://dx.doi.org/10.1182/blood-2018-99-111992.
Full textAbstract:
Abstract The prognosis of elderly patients (pts) with acute lymphoblastic leukemia (ALL) remains poor, and novel therapeutic approaches are clearly needed. CD19 is expressed on the majority of precursor-B ALLs and represents an attractive therapeutic target. The anti-CD19 bi-specific engager antibody blinatumomab has demonstrated significant activity in both relapsed/refractory ALL and minimal residual disease (MRD) positive ALL. Therefore, we evaluated blinatumomab as a single agent in the upfront treatment of newly diagnosed elderly pts with Philadelphia chromosome (Ph) negative B-lineage ALL to determine response rates and overall survival (OS). Methods: Pts were treated at National Clinical Trial Network sites from June 2015 to September 2017. The primary objective of the study was to estimate 3-year OS. An IND was approved by the FDA and the protocol was approved by a central institutional review board. Eligibility: age > 65 years, newly diagnosed Ph negative B-lineage ALL with adequate organ function and no evidence of central nervous system (CNS) disease. Pts received blinatumomab for induction at standard dosing for 1-2 cycles until attainment of complete response (CR) or CR with incomplete count recovery (CRi) (defined below). Pts then received 3 cycles of blinatumomab post-remission therapy followed by 18 months of maintenance POMP (prednisone, vincristine, 6-mercaptopurine, methotrexate). A total of 8 doses of intrathecal methotrexate were administered as CNS prophylaxis. Cytogenetic risk was ascribed by NCCN 2018 criteria and bone marrow samples were analyzed for the presence of the Ph-like signature. MRD was assessed centrally by 8 color flow cytometry pre-treatment, on Day 35 of induction cycle 1, and on Day 35 of re-induction (if applicable). Response was assessed at the completion of 1-2 cycles of blinatumomab. CR was defined as < 5% marrow blasts with no evidence of extramedullary disease and recovery of counts [absolute neutrophil count (ANC) > 1000/uL, platelets >100,000/uL]. CRi was defined the same as CR but ANC < 1000/ uL and/ or platelets ≤ 100,000/ uL. OS was measured from day of registration on trial until the date of death. Disease-free survival (DFS) was measured from the date the pt achieved CR/ CRi until relapse or death. Toxicities were graded according to NCI CTCAE version 4.0. Results: Of 31 pts enrolled, 29 were eligible. The median age was 75 years (range 66 - 84), 22 (76%) were male, median baseline white blood count was 3.7 x 103/uL (range 0.3 - 7,100), and median bone marrow blast count percentage was 86.5% (range 30-100). Three pts received hydroxyurea or steroids prior to treatment initiation. Cytogenetic risk at diagnosis was: poor (34% of pts; n=10), standard (55% of pts; n=16), good (3% of pts; n=1) and unknown (7% of pts, n=2). Testing for the Ph-like signature is being completed. The most common Grade 3-5 non-hematologic toxicities related to treatment during induction were hyperglycemia (14%), dyspnea (10%), febrile neutropenia (10%), hypertension (10%), and lung infection (7%). One pt developed Grade 3 cytokine release syndrome and 1 developed Grade 3 neurotoxicity. No pts died during the first 28 days of treatment. The overall response rate (CR + CRi) was 66% (all CRs). Thirteen of the 19 responders have available MRD data post-treatment. Of these, 12 pts (92%) achieved MRD negativity, all at Cycle 1 Day 35. One pt required 2 cycles of blinatumomab to achieve CR. One pt proceeded to allogeneic hematopoietic stem cell transplant. The median follow-up time is 1 year and median duration on trial is 170 days (6 pts are still on maintenance therapy). OS estimated by Kaplan Meier at 6 months is 79% (95% CI 58%-90%) and at 1 year is 65% (95% CI 43%-80%). DFS estimated at 6 months is 68% (95% CI 43%-84%) and at 1 year is 56% (95% CI 31%-75%). No baseline features including CD19 expression (by percentage or mean-fluorescent intensity) or presence of a CD19 negative subpopulation were associated with response. Conclusions: Blinatumomab was well tolerated and effective in the treatment of newly diagnosed elderly patients with Ph negative B-lineage ALL. Further follow up will determine the durability of these responses. Disclosures Advani: Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy. Wieduwilt:Leadiant: Research Funding; Merck: Research Funding; Shire: Research Funding; Reata Pharmaceuticals: Equity Ownership; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Park:Adaptive Biotechnologies: Consultancy; Pfizer: Consultancy; AstraZeneca: Consultancy; Novartis: Consultancy; Kite Pharma: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shire: Consultancy. Stock:Jazz Pharmaceuticals: Consultancy. Erba:Immunogen: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Juno: Research Funding; Juno: Research Funding; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Takeda/Millenium: Research Funding; Incyte: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Jazz: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Agios: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Amgen: Research Funding; Agios: Consultancy, Speakers Bureau; Astellas: Research Funding; MacroGenics: Consultancy; Takeda/Millenium: Research Funding; Seattle Genetics: Consultancy, Research Funding; MacroGenics: Consultancy; Novartis: Consultancy, Speakers Bureau; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Janssen: Research Funding; Celgene: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Janssen: Research Funding; Jazz: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Amgen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Pfizer: Consultancy, Other: grant; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Astellas: Research Funding; Pfizer: Consultancy, Other: grant; Celgene: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: grant; Incyte: Consultancy, Speakers Bureau; Juno: Research Funding; Jazz: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: grant; Astellas: Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Juno: Research Funding; Jazz: Consultancy, Speakers Bureau.
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Tosetto, Alberto, Zahra Badiee, Mohammad-Reza Baghaipour, et al. "Clustering of Bleeding Symptoms in Patients Previously Diagnosed As Type 3 Von Willebrand Disease: Results from a Large Cohort of Type 3 Von Willebrand Disease (the 3Winters-Ips Project)." Blood 132, Supplement 1 (2018): 2465. http://dx.doi.org/10.1182/blood-2018-99-113996.
Full textAbstract:
Abstract Patients with type 3 von Willebrand Disease (VWD) usually have markedly reduced FVIII/VWF levels and very severe bleeding manifestations but, because of their rarity, their bleeding phenotype is poorly described. We aimed at evaluating the distribution of bleeding symptoms in patients with type 3 VWD, comparing them with previously available data from a cohort of type 1 patients, and describing site-specific clustering of bleeding symptoms in these patients. We analyzed clinical data from the type 3 Von Willebrand International RegistrieS Inhibitor Prospective Study (3WINTERS-IPS),a no-profit, investigators initiated, multicenter, European-Iranian observational, retrospective and prospective study on patients with diagnosis of type 3 VWD. Aims of the 3WINTERS-IPS is 3-fold: a) to identify the main phenotypic and molecular characteristics of a large cohort of VWD patients; b) to evaluate the risk factors responsible for the severe bleeding phenotype; c) to assess the efficacy and safety of the treatment with VWF concentrates with or without FVIII including the risk of anti-VWF antibodies. Retrospective information on bleeding symptoms at presentation was collected using the MCMDM-1 VWD bleeding questionnaire, and bleeding severity summarized as bleeding score. Individual bleeding symptoms were considered as relevant when having a score >1 (hence requiring medical attention). Data was compared with that retrieved from the MCMDM-1 VWD study database on patients affected by type 1 VWD (index cases and affected family members). The study enrolled a total of 260 patients, of which we analysed 243 patients with available bleeding score at recruitment. The median age at study inclusion was 29 years (interquantile range, 26.5 years); 140 were females (53.8%). There were 108 patients of Iranian descent, while the remaining of patients were from Europe. The median number of bleeding symptoms was 5, and the median bleeding score was 15 (interquantile range, 13). Only 7/243 patients (2.8%) had a single bleeding symptom. Epistaxis was the most frequent relevant symptom, being present in 195 patients (80.2%), followed by menorrhagia in 99 females (70.7%). Males had a higher frequency of hemarthroses and hematomas than females (53.4% vs 42.1% and 40.8% vs 27.1%, respectively). When comparing the clinical presentation of type 3 vs. type 1 VWD, clearly increased bleeding scores were evident for all age-classes and even in paediatric cases. The association between symptoms having a relative frequency >20% is presented in the circle diagram, showing that some symptoms appeared to cluster with others in a variable degree (e.g., menorrhagia with epistaxis, hemarthrosis or oral cavity bleeding; post-extraction bleeding again with epistaxis, hemarthrosis or oral cavity bleeding; surgical bleeding or gastrointestinal bleeding with epistaxis alone). These findings confirm the severity of type 3 VWD and extend the knowledge of symptoms distribution in the widest available cohort of type 3 VWD patients. Disclosures Tosetto: Stago, Novo-Nordisk, BMS: Speakers Bureau; Werfen: Other: Member of Advisory Board, Speakers Bureau. Berntorp:Octapharma: Consultancy; CSL Behring: Consultancy; Shire: Consultancy, Other: honoraria for lecturing . Eikenboom:CSL: Research Funding. Mazzucconi:Baxalta-Shire: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis,: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau. Oldenburg:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Peyvandi:Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Shire: Speakers Bureau; Roche: Speakers Bureau; Shire: Speakers Bureau; Kedrion: Consultancy; Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Roche: Speakers Bureau; Octapharma US: Honoraria; Octapharma US: Honoraria; Sobi: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Kedrion: Consultancy; Shire: Speakers Bureau; Roche: Speakers Bureau; Roche: Speakers Bureau; Novo Nordisk: Speakers Bureau; Shire: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Shire: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Novo Nordisk: Speakers Bureau; Octapharma US: Honoraria; Octapharma US: Honoraria; Sobi: Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Kedrion: Consultancy; Sobi: Speakers Bureau; Roche: Speakers Bureau; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Sobi: Speakers Bureau; Octapharma US: Honoraria; Sobi: Speakers Bureau. Schneppenheim:SHIRE: Consultancy; CSL Behring: Consultancy. Tiede:Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Consultancy; Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Honoraria; Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Research Funding.