Journal articles: 'United States. Bureau of Corporations'

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Parasuraman, Shreekant V., Ahmad B. Naim, Dilan C. Paranagama, Maureen Thyne, Sara Goldberger, John O. Mascarenhas, James Mangan, Salman Fazal, Carole B. Miller, and Ruben A. Mesa. "Financial Burden of Myeloproliferative Neoplasms on Patients: Results from the MPN Landmark Survey in the United States." Blood 126, no. 23 (December 3, 2015): 5561. http://dx.doi.org/10.1182/blood.v126.23.5561.5561.

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Abstract Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms (MPNs). Patients across all 3 MPNs experience marked disease burden in terms of symptoms and negative effects on quality of life (QoL), productivity, and activities of daily living (ADL). To improve the lives and health of patients with MPNs, it is also important to have a current understanding of these burdens from a financial standpoint. This analysis of MPN Landmark survey data examined the financial burden of patients who reported that their MPN affected their employment (ie, reduced work hours, discontinued employment, or went on medical disability) or experienced no such effects on their employment. Methods: Patients diagnosed with MF, PV, or ET were recruited to participate in a real-world retrospective study (MPN Landmark survey) in the US (fielded May - July 2014). Only respondents who were diagnosed before 2013 and were 16 to 65 years of age at the time of diagnosis were eligible for this analysis. Participants were asked if their MPN had an impact in terms of reduced work hours, discontinued employment, medical disability, or no impact; the first 3 categories were not mutually exclusive. Participants provided information on their annual household income in 2013 before taxes by selecting from the following categories: ≤$15,000, $15,001-$25,000, $25,001-$35,000, $35,001-$50,000, $50,001-$75,000, $75,001-$100,000, and >$100,000. The mid value of each range was used to calculate mean income levels within each subgroup evaluated. Results: A total of 813 patients completed the web-based Landmark survey and 369 eligible patients were included in this analysis (MF, 85; PV, 172; ET, 112). Median age among patients with ET was slightly lower than among patients with MF and PV at time of MPN diagnosis (ET, 48 years; MF, 56 years; PV, 53 years). The majority of respondents were women (MF, 62%; PV, 52%; ET, 75%). Almost all patients (99%) had health insurance, primarily group commercial insurance through an employer (MF, 46%; PV, 53%; ET, 57%) and Medicare (MF, 40%; PV, 34%; ET, 24%). Most patients had at least some college education (ie, some college, 4-year degree, or postgraduate degree): MF, 86%; PV, 90%; ET, 88%. The mean 2013 household income of patients with MF, PV, and ET were similar to each other ($79,800, $80,200, and $80,400, respectively) and slightly higher than the total 2013 US mean household income of $75,839. A notable proportion of patients in each MPN group reported that their disease led to reduced work hours, discontinued employment, and medical disability: MF, 38%, 35%, and 33%, respectively; PV, 33%, 28%, and 15%; ET, 28%, 21%, and 4%. Patient demographics, such as age and health insurance status, were similar among patients who reported MPN-associated effects on employment and patients who did not within each MPN. In each MPN group, the mean percentage household income loss in patients with reduced work hours, discontinued employment, and medical disability were: MF, 16%, 18%, and 28%, respectively; PV, 15%, 24%, and 17%; and ET, 0%, 24%, and 37%, compared with patients who did not experience any effects of their MPN on employment (Figure 1). Discontinued employment and medical disability tended to have a greater impact compared with reduced work hours across MPNs. Conclusion: Patients withMPNs may experience a considerable negative impact on their employment status, which in turn may be associated with reduced annual household income. Therefore, across all MPNs, forestalling or reversing discrete aspects of the diseases that negatively impact individual productivity is an important factor in the management of these chronic neoplasms. Disclosures Parasuraman: Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte Corporation: Employment, Equity Ownership. Thyne:Incyte Corporation: Speakers Bureau. Mascarenhas:Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Kalobios: Research Funding. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Miller:Incyte Corporation: Honoraria, Research Funding. Mesa:Promedior: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Pfizer: Research Funding.

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Fazal, Salman, Carole B. Miller, John O. Mascarenhas, Maureen Thyne, Sara Goldberger, Dilan C. Paranagama, Shreekant V. Parasuraman, Ahmad B. Naim, James Mangan, and Ruben A. Mesa. "Phlebotomy Frequency and Quality of Life and Productivity in Patients with Polycythemia Vera: Results from the MPN Landmark Survey in the United States." Blood 126, no. 23 (December 3, 2015): 5184. http://dx.doi.org/10.1182/blood.v126.23.5184.5184.

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Abstract Background: Phlebotomy is a common and established treatment in patients diagnosed with polycythemia vera (PV) to reduce the risk of thromboembolic events, in both acute and chronic settings. However, phlebotomy may not alleviate all PV-related symptoms and its frequent application can cause moderate to profound iron deficiency, which may worsen PV-related symptoms. This analysis of MPN Landmark survey data examined patient-reported quality of life (QoL) and productivity outcomes in patients with PV based on phlebotomy treatment history. Methods: Patients who were diagnosed with a myeloproliferative neoplasm (MPN) were recruited to participate in the MPN Landmark survey in the US (fielded May - July 2014). This analysis describes responses from patients with PV on questions regarding PV-related symptom burden, QoL, and productivity. Patient responses were analyzed based on phlebotomy treatment history and included patients who were actively receiving phlebotomy within the last 3 months (≥1 per month, every other month, and every 3 months or longer), had discontinued phlebotomy, or were phlebotomy-naive. Descriptive statistical analyses were used to evaluate these outcomes based on phlebotomy frequency, as appropriate. Results: Overall, 813 patients completed the Landmark survey, and 274 out of the 380 patients with PV who completed the survey were evaluable for this analysis. Mean age ranged from 61.6-65.4 years among phlebotomy subgroups (Table 1). The average duration of PV was longest among patients with PV who had discontinued phlebotomy (12.0 years) compared with phlebotomy-naive patients (6.3 years) and patients actively treated with phlebotomy (5.9-8.9 years). The percentage of patients diagnosed within 1 year of the survey ranged from 4.1% to 11.5% among the patients who had been treated with phlebotomy and was 15.4% in the phlebotomy-naive subgroup. Most patients reported PV-related symptoms; symptom burden was similar in all phlebotomy subgroups. Fatigue was the most common symptom reported in all subgroups (range, 71.4%-80.8%). QoL measures were generally worse with higher phlebotomy frequency (Table 1). Similarly, more frequent phlebotomy procedures was found to be associated with reduced productivity: patients who received ≥1 phlebotomy per month had the highest mean number (in the preceding 30 days) of sick days (among patients employed), days spent in bed, and days with plans canceled. Of note, approximately one third of patients receiving more frequent phlebotomy procedures were also receiving concomitant hydroxyurea to manage their PV (≥1 per month, 38.5%; every other month, 36.4%). Conclusion: Patients with PV may experience disease-related symptoms and reductions in QoL and work productivity. Frequent phlebotomy procedures were associated with increasingly worsened QoL and decreased work productivity. Further research is needed to better understand the impact of phlebotomy on patient-reported outcomes in patients with PV. Disclosures Fazal: Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Miller:Incyte Corporation: Honoraria, Research Funding. Mascarenhas:Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Kalobios: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Incyte Corporation: Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Paranagama:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Mesa:Promedior: Research Funding; Genentech: Research Funding; Gilead: Research Funding; NS Pharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; CTI Biopharma: Research Funding; Pfizer: Research Funding; Incyte Corporation: Research Funding.

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Verstovsek, Srdan, Shreekant Parasuraman, Jingbo Yu, Anne Shah, Shambhavi Kumar, Ann Xi, and Claire Harrison. "Real-World Survival Among Patients with Intermediate- to High-Risk Myelofibrosis in the United States: Impact of Ruxolitinib Approval." Blood 136, Supplement 1 (November 5, 2020): 46–47. http://dx.doi.org/10.1182/blood-2020-140820.

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Background The myeloproliferative neoplasm myelofibrosis (MF) is associated with reduced overall survival (OS) compared with the general population (Hultcrantz M, et al. J Clin Oncol. 2012;30[24]:2995-3001; Price GL, et al. PLoS One. 2014;9[3]:e90299). The Janus kinase 1 and 2 inhibitor ruxolitinib (RUX) was approved by the US Food and Drug Administration in November 2011 for the treatment of adult patients with intermediate- or high-risk MF based on data from the phase 3 COMFORT trials, which showed significantly improved OS in patients who received RUX (Verstovsek S, et al. J Hematol Oncol. 2017;10:156). Understanding the clinical benefit of RUX in real-world practice requires an understanding of changes in patient outcomes for those exposed to RUX compared with those never exposed to RUX, both before and after approval. The aim of this analysis was to assess the OS of patients newly diagnosed with intermediate- to high-risk MF before RUX approval, and for those who were RUX-unexposed vs -exposed in the post-RUX approval time frame. Study Design and Methods All data from the Medicare Fee-for-Service claims database (Parts A/B/D) from January 2010 to December 2017 were used to identify patients who were ≥65 years old (intermediate-1 or higher risk MF due to age) with ≥1 inpatient claim or ≥2 outpatient claims with a documented MF diagnosis. The index date was the date of the first qualifying MF claim; ≥12 months of pre-index continuous medical and pharmacy enrollment was required. Patients with evidence of an MF diagnosis ≤12 months before the index date were excluded. Patients with a diagnosis of myelodysplastic syndrome, hematologic malignancies (leukemias, multiple myeloma, and lymphomas), or solid tumors either ≤12 months before, on, or any time after index were also excluded in a stepwise manner. The study sample was classified into 3 groups: patients diagnosed with MF pre-RUX approval (index year 2010-2011; no post-index exposure to RUX); those diagnosed with MF post-RUX approval and unexposed to RUX (index year 2012-2017); and those diagnosed with MF post-RUX approval and exposed to RUX (index year 2012-2017). One-year survival rate and risk of mortality were estimated using Kaplan-Meier and Cox proportional hazards regression analyses, adjusting for baseline demographic and clinical characteristics. OS was measured from the index date until death or end of follow-up. Patients without a death date were censored at disenrollment or the end of the study period, whichever occurred first. Results Among eligible patients with an MF diagnosis (N=1677), median age was 78 years, 39.8% were male, and 84.1% were white. The analysis included 278 patients diagnosed pre-RUX approval (all RUX-unexposed) and 1399 diagnosed post-RUX approval (RUX-unexposed, n=1127; RUX-exposed, n=272). Median follow-up for the pre- and post-RUX approval groups was 12.5 and 11.3 mo (RUX-unexposed, 10.2 mo; RUX-exposed, 14.0 mo), respectively. In the pre-RUX approval group, 119 (42.8%) patients had a valid death date compared with 436 (31.2%) in the post-RUX approval group (RUX unexposed, n=382 [33.9%]; RUX exposed, n=54 [19.9%]). The 1-year survival rate (95% CI) was 55.6% (49.4%-61.3%) for the pre-RUX approval group, 72.5% (69.5%-75.2%) for the post-RUX approval RUX-unexposed group, and 82.3% (76.7%-86.7%) for the post-RUX approval RUX-exposed group (Figure). The risk of mortality was lowest among RUX-exposed patients (adjusted hazard ratio [HR], 0.36; 95% CI, 0.26-0.50; P<0.0001 vs the pre-RUX approval group). Patients in the post-RUX approval group who had never been exposed to RUX also had a lower risk of mortality, although less pronounced than RUX-exposed patients, compared with the pre-RUX approval group (adjusted HR, 0.67; 95% CI, 0.56-0.80; P<0.0001). Conclusions In this real-world study of US patients diagnosed with intermediate- or high-risk MF, 1-year OS was improved in patients diagnosed after RUX approval compared with before RUX approval. Notably, in the post-RUX approval time frame, 1-year OS was greater for those who received RUX than for those who did not receive RUX. These findings complement the survival benefit results demonstrated in the COMFORT studies using real-world data. Disclosures Verstovsek: Gilead: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding; Incyte Corporation: Consultancy, Research Funding; CTI Biopharma Corp: Research Funding; Celgene: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; AstraZeneca: Research Funding; ItalPharma: Research Funding; Protagonist Therapeutics: Research Funding; PharmaEssentia: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Roche: Research Funding; Promedior: Research Funding. Parasuraman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Shah:Avalere Health: Current Employment. Kumar:Avalere Health: Current Employment; Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation. Xi:Avalere Health: Current Employment; Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation. Harrison:Gilead Sciences: Honoraria, Speakers Bureau; CTI Biopharma Corp: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria; Sierra Oncology: Honoraria; Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Incyte Corporation: Speakers Bureau; AOP Orphan Pharmaceuticals: Honoraria; Promedior: Honoraria.

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Mesa, Ruben A., Carole B. Miller, John O. Mascarenhas, Maureen Thyne, Sara Goldberger, Dilan C. Paranagama, Shreekant V. Parasuraman, Salman Fazal, Ahmad B. Naim, and James Mangan. "Hydroxyurea Treatment History and Quality of Life in Patients with Polycythemia Vera: Results from the MPN Landmark Survey in the United States." Blood 126, no. 23 (December 3, 2015): 4077. http://dx.doi.org/10.1182/blood.v126.23.4077.4077.

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Abstract Background: Patients with the myeloproliferative neoplasm (MPN) polycythemia vera (PV) require treatment to manage blood cell counts and reduce the risks of cardiovascular/thromboembolic events. Hydroxyurea (HU) is a common cytoreductive treatment; however, some patients discontinue HU treatment because of resistance, intolerance, or frequently a combination of both limitations. Patients may also continue to receive HU despite diminishing or nonexistent clinical benefit, sometimes in combination with persistent need for phlebotomy procedures. This analysis of MPN Landmark survey data examined patient-reported quality of life (QoL) outcomes in patients with PV who were naive to HU (HU-N), were continuing HU (HU-C), or had discontinued HU (HU-D). Methods: Patients with an MPN under active management in the US were eligible to complete an online survey (fielded May - July 2014). This is a report of responses given by patients with PV to questions about symptom burden, QoL, activities of daily living (ADL), and work/productivity. PV-related effects on patients feeling depressed/discouraged, patients feeling anxious/worried, or interference with ADLs were considered to be at high levels if the patient-reported score was ≥4 on a scale of 1 (not at all) to 5 (a great deal). Symptom severity was rated on a scale of 0 (absent) to 10 (worst imaginable). Results: The survey respondents included 380 patients with PV (HU-N, n=159; HU-C, n=181; HU-D, n=40). Mean age was 62.2 years, 65.1 years, and 64.2 years in the HU-N, HU-C, and HU-D groups, respectively. Mean duration of PV was 8.3 years, 10.3 years, and 13.9 years in the HU-N, HU-C, and HU-D groups, respectively. Patients who had not received HU were currently or previously treated with phlebotomy (87.4%), interferon (11.3%), or anagrelide (9.4%); 66.0% of HU-N patients were classified as high-risk based on information provided by the patients in the survey (ie, age 60 or older or history of thrombosis). Among HU-C and HU-D patients, treatment history included phlebotomy (89.5% and 100%, respectively), interferon (7.2% and 52.5%), or anagrelide (15.5% and 35.0%); 79.6% and 82.5%, respectively, were classified as high-risk. Ruxolitinib was not FDA-approved for PV at the time of this survey. Patients reported high levels of feeling anxious/worried and depressed/discouraged as a result of their PV across all subgroups: HU-N, 27.7% and 15.1%, respectively; HU-C, 22.7% and 15.5%; HU-D, 32.5% and 22.5%. Many patients also experienced a high level of PV-related interference with ADLs, which was more common in the HU-D group (30.0%) than the HU-N (11.3%) or HU-C (18.2%) groups. HU-D patients were more likely to have reported ever reducing their work hours (54.2% of the patients who responded) compared with the HU-N (33.3%) and HU-C groups (36.8%). Among all patients, HU-D patients reported a mean of 8.3 doctor visits in the past 12 months, compared with 5.6 in the HU-N group and 6.6 in the HU-C group. Most patients had experienced PV-related symptoms in the past 12 months (Table 1), particularly fatigue, itching, and day/night sweats; fatigue was ranked first as the symptom that patients would most like to resolve. Conclusion: Patients with PV in a large retrospective real-world survey across the US are found to experience burdensome PV-related symptoms and reduced QoL. The findings from this study also show that standard treatments do not address these aspects of PV in many patients, and patients who have discontinued HU may experience an even greater disease burden, possibly because of a lack of effective and/or safe alternative treatment options. Importantly, while 66.0% of the patients in the HU-N group were classified as high-risk, the majority of the high-risk patients in the HU-N group (81.0%) were not treated with cytoreductive agents, suggesting a potential knowledge deficit regarding recommendations for PV management. Collectively, these results illustrate the adverse impact of PV-related symptom burden on patient QoL and reinforce the importance of unmet control of PV-related symptoms in choosing PV therapy. Disclosures Mesa: Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Promedior: Research Funding; Gilead: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Mascarenhas:Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Kalobios: Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Paranagama:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Naim:Incyte Corporation: Employment, Equity Ownership. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

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Mesa, Ruben, Carole B. Miller, Maureen Thyne, James Mangan, Sara Goldberger, Salman Fazal, Xiaomei Ma, et al. "Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Overall Health and Productivity: Results from the MPN LANDMARK SURVEY in the United States." Blood 124, no. 21 (December 6, 2014): 3183. http://dx.doi.org/10.1182/blood.v124.21.3183.3183.

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Abstract Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), are chronic MPNs associated with a broad array of symptoms that may negatively impact patients’ quality of life (QoL). To enhance patient care, it is important to have a current and clear understanding of how MPNs affect the overall health and daily lives of patients. The MPN LANDMARK SURVEY was developed to examine patients’ perceptions of these MPNs related to disease burden, QoL, productivity, and activities of daily living (ADLs). Methods: Eligible patients diagnosed with an MPN were recruited to participate in an online survey conducted from May–July 2014in the US. Patients were asked about the overall burden of disease and impact of symptoms on their QoL, productivity, and ADLs. Descriptive analyses were conducted to assess these outcomes and examined by calculated (not reported) prognostic risk score (MF - DIPSS: Passamonti, Blood 2010; PV: Tefferi, Leuk 2013; ET - IPSET: Passamonti, Blood 2012) and symptom severity quartiles, which were determined using the MPN Symptom Assessment Form (MPN-SAF) total symptom scores. Results: 813 patients (MF=207; PV=380; ET=226) responded to the survey. A majority of patients were female (MF, 54%; PV, 62%; ET, 72%), approximately half were aged 60–74 years (MF, 55%; PV, 51%; ET, 46%), and most were covered by health insurance (>98%). Nearly half (48%) were diagnosed within the last 5 years and average time to diagnosis from first symptoms was >2 years. A high proportion of patients had intermediate to high prognostic risk scores (MF, 94%; PV, 87%; ET, 44%). The majority of patients reported feeling anxious or worried about their MPN (MF, 91%; PV, 78%; ET, 74%). Among all groups, fatigue was the most severe symptom reported (mean MPN-SAF score=6.0–6.4 on a scale of 0–10). A subset of patients in each group described their symptoms as very severe (severity score ≥7 on a scale of 0–10; MF: fatigue [59%], problems with sexual desire [49%], inactivity [46%]; PV: inactivity [48%], fatigue [49%], problems with sexual desire [49%]; and ET: problems with sexual desire [49%], fatigue [50%], headaches [40%]). The majority of patients reported that MPN-related symptoms reduced their QoL (MF, 81%; PV, 66%; ET, 57%); this was reported in all risk groups but more frequently by patients with a high risk score vs a low risk score in MF and ET (MF, 89% vs 69%; PV, 63% vs 65%; ET, 71% vs 59%). A more substantial QoL impact was reported by patients in high vs low symptom quartiles (MF, 95% vs 51%; PV, 94% vs 33%; ET, 93% vs 15%). Similarly, MPNs also had a marked negative impact on reduced work hours, sick days, voluntary job termination, receipt of medical disability, early retirement, and ADLs (Table 1). For example, among patients employed, approximately one fourth reported missing ≥1 day of work (MF, 29%; PV, 19%; ET, 23%) in the last 30 days before the survey. Even patients with low prognostic risk scores often reported missing ≥1 day of work (MF, 33%; PV, 23%; ET, 22%) or cancelling ≥1 day of planned activities (MF, 46%; PV, 35%; ET, 34%). Patients in the high vs low symptom quartiles were more likely to call in sick to work (MF, 48% vs 0%; PV, 52% vs 4%; ET, 38% vs 0%) or cancel ≥1 day of planned activities (MF, 77% vs 5%; PV, 56% vs 7%; ET, 67% vs 3%). Conclusion: The findings from this large, first-of-its-kind survey demonstrate a marked burden of disease across all 3 MPNs that is not limited to symptoms but extends to QoL, productivity, and ADLs. Although high prognostic risk scores have long been associated with a significant burden of disease, in this study, patients with a low risk score also reported significant burden. The symptom burden reported is consistent with previous studies, thus validating the present dataset. MPN treatment considerations should include reducing the symptom burden and improving QoL and productivity to enhance the overall health and lives of MPN patients. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Incyte Corporation: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.

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Shah, Nirmish, Ralph Boccia, Walter K. Kraft, Brandon M. Hardesty, Jincy Paulose, Dram Laine, Das Purkayastha, Savita Nandal, and Abdullah Kutlar. "A Multicenter Retrospective Noninterventional Follow-up Study in Patients with Sickle Cell Pain Crisis Who Previously Participated in the Sustain Trial in the United States Successor Study." Blood 132, Supplement 1 (November 29, 2018): 4910. http://dx.doi.org/10.1182/blood-2018-99-111332.

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Abstract INTRODUCTION SUSTAIN was a randomized, double-blind, placebo-controlled, phase 2, 52-week study that compared the effect of crizanlizumab, a P-selectin inhibitor, versus placebo on the frequency of sickle cell pain crises (SCPCs, or vaso-occlusive crises [VOCs] leading to a health care visit) in patients with any genotype of sickle cell disease (SCD). Crizanlizumab 5.0 mg/kg significantly reduced the annual frequency of VOCs versus placebo (1.6 vs 3.0, P=0.01) and increased the time to first on-treatment VOC (4.1 vs 1.4 months, P=0.001). The current study, SUCCESSOR (SUSTAIN Chart-review of Crizanlizumab to Evaluate Sickle-cell Study One-year Retrospective), reviewed medical records of patients who completed the SUSTAIN study at US sites to assess additional cases of significant pain crisis events, and to generate real-world data on treatment patterns and health care resource utilization upon completion of treatment with crizanlizumab. METHODS SUCCESSOR is a retrospective cohort study of adult patients (≥18 years old) who participated in the SUSTAIN study in the United States to evaluate outcomes related to SCD up to 52 weeks following their completion of the trial. SUCCESSOR included the per protocol population from SUSTAIN, which included the intent-to-treat patients who received at least 12 of the 14 planned study drug doses, completed a visit at least 14 days after the final dose of study drug, and had no major protocol violations that impacted the efficacy assessments. The overall study period for the retrospective study was from September 2015 to March 2017 and patient data were obtained from medical records. Crizanlizumab was not administered post-SUSTAIN. Patient consent was obtained prior to data collection if required by local and/or central research ethics review. RESULTS In this preliminary analysis, a total of 6 patient data sets were extracted. These patients had been randomized to the following treatment arms in the SUSTAIN study: 1 placebo, 1 crizanlizumab 2.5 mg/kg, and 4 crizanlizumab 5.0 mg/kg. The patient who had received placebo during SUSTAIN was a 27-year-old male with HbS/β0-thalassemia SCD. The patient who had received crizanlizumab 2.5 mg/kg was a 42-year-old female with HbSC SCD. The patients who had received crizanlizumab 5.0 mg/kg were: a 28-year-old male with HbSS SCD; a 32-year-old female with HbSS SCD; a 56-year-old female with HbSC SCD; and a 65-year-old female with HbSS SCD. All patients were Black or African-American. In the 52 weeks following completion of the SUSTAIN study, patients who had received placebo or crizanlizumab 2.5 mg/kg reported 4 and 5 VOC events, respectively, while crizanlizumab 5.0 mg/kg patients reported 0-2 VOC events (Table). Four patients (3 crizanlizumab 5.0 mg/kg, 1 placebo) reported hydroxyurea (HU) usage during and after SUSTAIN. One patient who had received crizanlizumab 5.0 mg/kg and did not report HU usage during SUSTAIN reported HU usage post-SUSTAIN. All patients reported opioid usage after SUSTAIN. Transfusions were not allowed during SUSTAIN; 2 patients, 1 who had received crizanlizumab 5.0 mg/kg and 1 who had received placebo, reported transfusions post-SUSTAIN. Five of the 6 patients reported utilizing health care resources (eg, clinic visits, emergency department visits, or hospitalizations) post-SUSTAIN. One patient who received crizanlizumab 5.0 mg/kg did not report utilizing any health care resources post-SUSTAIN and did not report any VOC events in the 52 weeks after SUSTAIN. CONCLUSIONS We report our initial results from a limited number of patients from SUCCESSOR and therefore summarized post-SUSTAIN outcomes without analysis. In 5 of the 6 patients, the annual frequency of VOC events remained the same or increased in the post-SUSTAIN period compared to that during the SUSTAIN study. Data collection is ongoing in additional eligible patients. Disclosures Shah: Novartis: Consultancy, Research Funding, Speakers Bureau. Boccia:Amgen: Honoraria, Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; BMS: Research Funding, Speakers Bureau. Hardesty:Biomarin: Research Funding; Bioverativ: Research Funding; Global Blood Therapeutics: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Prometic: Research Funding; Sangamo: Research Funding; Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Paulose:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Laine:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Purkayastha:Novartis Pharmaceuticals Corporation: Employment. Nandal:Novartis Pharmaceuticals Corporation: Employment. Kutlar:Sancilio: Other: DSMB Chair; Bluebird Bio: Other: DSMB Member; Novartis: Consultancy, Honoraria, Other: Personal fees, Research Funding.

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Hari, Parameswaran, Haris Ali, Yi-Bin Chen, Salman Fazal, Tara K. Gregory, Sarah M. Anand, Ahmad Naim, et al. "Safety Analysis of Patients Who Received Ruxolitinib for the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease in an Expanded Access Program." Blood 136, Supplement 1 (November 5, 2020): 39–40. http://dx.doi.org/10.1182/blood-2020-140541.

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Background Graft-versus-host disease (GVHD) is a serious, potentially fatal complication of allogeneic hematopoietic cell transplantation (HCT). Ruxolitinib (RUX), a Janus kinase (JAK) 1/JAK2 inhibitor, is in phase 3 development for patients (pts) with steroid-refractory chronic GVHD (SR cGVHD), and is approved for the treatment of steroid-refractory acute GVHD (SR aGVHD) in the United States. Outside of clinical trials, access to RUX is provided to pts with SR cGVHD through an expanded access program (EAP) sponsored by Incyte Corporation in the United States. The primary objective of this analysis was to report safety data from pts with SR cGVHD who received RUX in the Incyte-sponsored US EAP. Study Design and Methods Patients eligible to enroll in the open-label, multicenter US EAP from September 2017-May 2020 were ≥12 years of age, developed SR aGVHD or SR cGVHD after allogeneic HCT, and had an ECOG PS of 0-3. Pts with SR aGVHD and those with incomplete or missing data were excluded from the analysis. Based on clinical experience, the recommended starting dose of oral RUX for pts with cGVHD was 10 mg twice daily (BID). Doses could not be escalated above 10 mg BID, but dose reductions were permitted during treatment based on safety and laboratory assessments. The dose of RUX could be re-escalated if toxicity management thresholds were met or if pts experienced GVHD flares and had adequate hematologic parameters. Any GVHD treatments received before RUX initiation were recorded, and concurrent therapy with other cGVHD treatments was permitted. Serious adverse events (SAEs) were assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 from the time of consent until 30 days after end of treatment. Pt characteristics, prior treatments, and RUX dosing were summarized using descriptive statistics. Overall survival (OS) was assessed using Kaplan-Meier methodology. Results The analysis included 481 pts with SR cGVHD and complete data (data cutoff, 08 May 2020). Median (range) age was 60.0 (15-81) years; 51.8% of pts were male. At the time of RUX initiation, the organs involved included the skin (70.7%), eyes (59.3%), mouth (55.7%), joints (38.0%), lungs (34.9%), gastrointestinal tract (28.1%), liver (18.9%), and genitals (11.0%). Most pts (65.3%) received ≥2 prior treatments for GVHD, including systemic corticosteroids (54.9%), calcineurin inhibitors (25.6%), sirolimus (20.8%), mycophenolate mofetil (14.6%), ibrutinib (7.1%), and RUX (3.1%); 26.6% of pts received topical corticosteroids and 12.3% received other topical treatments. Most pts initially received RUX 5 mg BID (n=228 [47.4%]) or 10 mg BID (n=229 [47.6%]); 276 pts (57.4%) received RUX 10 mg BID as their last dose at the time of discontinuation or data cutoff. At data cutoff, 332 pts (69.0%) were still receiving RUX. Primary reasons for treatment discontinuations were death (7.1%), GVHD progression (5.4%), malignancy relapse (3.5%), and adverse events (2.5%). The median (range) duration of RUX treatment was 7.2 (0.03-33.0) months. SAEs, regardless of causality, were reported in 162 pts (33.7%). Median (range) time to first SAE from RUX initiation was 77.0 (1-693) days. The most common SAEs were sepsis (n=18 [3.7%]), pyrexia (n=9 [1.9%]), dyspnea (n=8 [1.7%]), respiratory failure (n=8 [1.7%]), acute kidney injury (n=7 [1.5%]), failure to thrive (n=7 [1.5%]), influenza (n=7 [1.5%]), diarrhea (n=6 [1.2%]), fall (n=6 [1.2%]), pulmonary embolism (n=6 [1.2%]), and upper respiratory tract infection (n=6 [1.2%]). One pt (0.2%) had a cytomegalovirus viremia SAE. There were few SAEs reported for cytopenias (febrile neutropenia, n=2 [0.4%]) or fungal infections (fungal pneumonia, n=1 [0.2%]); SAEs for neoplasms were reported for 8 pts (1.7%). There were no SAEs of thrombotic microangiopathy. Forty-six pts (9.6%) had fatal SAEs, most commonly attributed, at least in part, to infections (n=13 [28.3% of SAE-related fatalities]). Thirty-six pts (7.5%) had SAEs deemed related to RUX. The OS rates (95% CI) were 88% (84-91) at 1 year and 82% (74-88) at 2 years (Figure). Conclusions Patients with SR cGVHD in the RUX EAP program were heavily pretreated and primarily had organ involvement of the skin, eyes, and mouth. SAEs were reported in one-third of pts, including 7% of pts with RUX-related SAEs. Ten percent of pts had fatal SAEs, primarily due to infectious complications of cGVHD. No new or unexpected SAEs were reported. Figure 1 Disclosures Hari: Incyte Corporation: Consultancy; Takeda: Consultancy; BMS: Consultancy; Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy. Ali:Incyte Corporation: Consultancy. Chen:Takeda: Consultancy; Incyte Corporation: Consultancy; Equillium: Other: Data and Safety Monitoring Board Member; Actinium: Other: Data and Safety Monitoring Board Member; Magenta: Consultancy; Kiadis: Consultancy; AbbVie: Other: Data and Safety Monitoring Board Member. Fazal:Agios: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Karyopham: Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Gregory:Bluebird: Research Funding; Celgene: Research Funding; BMS: Research Funding; CURIS: Research Funding; Celularity: Research Funding; Constellation: Research Funding; CRISP Therapeutics: Research Funding; Acetylon: Research Funding; AbbVie: Research Funding; Amgen: Research Funding; Incyte Corporation: Consultancy; Vivolux: Research Funding; Teva: Research Funding; Takeda: Research Funding; Sanofi: Research Funding; Poseida: Research Funding; Novartis: Research Funding; Kesios: Research Funding; Lilly: Research Funding; Janssen: Research Funding; Glenmark: Research Funding; Genentech: Research Funding; EMD Sorono: Research Funding. Anand:AltruBio: Research Funding; CSL Behring: Research Funding; Incyte Corporation: Research Funding; Equillium: Research Funding; Kadmon: Research Funding. Naim:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Paranagama:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Bhatt:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Blithe:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. DiPersio:Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Ruxolitinib is a JAK1/JAK2 inhibitor approved by the FDA for the treatment of adults with steroid-refractory acute GVHD. Ruxolitinib is in phase 3 testing for the treatment of steroid-refractory chronic GVHD but is currently not approved for this indication.

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Weinreb, Neal J., Deborah Barbouth, and Robert E. Lee. "Causes of Death in 184 Patients with Type 1 Gaucher Disease From the United States Who Were Never Treated with Enzyme Replacement Therapy." Blood 118, no. 21 (November 18, 2011): 3128. http://dx.doi.org/10.1182/blood.v118.21.3128.3128.

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Abstract Abstract 3128 Type 1 Gaucher disease (GD1) is caused by deficient lysosomal glucocerebrosidase activity with resultant accumulation of glucosylceramide predominantly within hepatic, splenic, pulmonary and bone marrow macrophages. Intravenous recombinant glucocerebrosidase (ERT) is generally safe and effective in decreasing morbidity due to the heterogeneous manifestations of GD1: hematological cytopenias, hepatosplenomegaly, bone pain, osteonecrosis, osteopenia and fractures. There are other complications whose responsiveness to conventional treatment is yet undetermined: atypical Parkinsonism and an increased risk for cancer (CA), particularly plasma cell and other hematological and lymphoid malignancies and hepatocellular carcinoma. Because of the widespread use of ERT during the past 20 years and attrition of older medical records, a phenotypically representative control group of untreated symptomatic patients for study of these late outcome events is hard to find. From 1961–97, one of us (REL) collected information on 395 US patients with GD1. We determined through public records that 217 died from 1950–2010 of whom 184 never received ERT. Here, we report confirmed causes of death (COD) for the untreated GD1 patients compared to COD reported for this time period in an age comparable overall US population. Methods: After IRB approval, COD recorded in death certificates were accessed via the National Death Index for available years 1979–2008. COD prior to 1979 were determined based on autopsy or physician communication with REL and, where possible, by death certificates obtained from State Bureaus of Vital Records. Information on COD (1950–2008) for the general US population is from US National Vital Statistics Reports. The analysis included descriptive statistics, calculation of proportional mortality ratios (PMR), and 2-tailed Fisher exact test calculations based on absolute death numbers in the GD1 and general populations. Results: COD is unknown for 9 patients who died before 1979. 111 pts were male (60.3%); 124 (67.4%) were Ashkenazi Jewish. Median age at death was 66y (2–97y). Median age at GD1 diagnosis (N=102): 39y (1–83y). Spleen status: Splenectomy 94 (51.1%); Intact 56 (30.4%); Unknown 34 (18.5%). Median age at splenectomy: 36y (1.3–78y). Symptomatic bone disease was present in 74 (40.2%), absent in 7 (3.8%) and undocumented for 103 (60.0%). COD for which the PMR was significantly increased (P<0.01): malignant neoplasms (PMR 1.57), suicide/drug overdose (PMR 3.86), chronic liver disease (PMR 4.76) and septicemia (PMR 9.22). Other COD that were disproportionately high included CNS and gastrointestinal bleeding, post-splenectomy complications, pulmonary hypertension (PHT), and Parkinsonism. Heart disease/atherosclerosis was the only COD for which PMR was very significantly decreased (0.33). PMR for cerebrovascular disease was 0.48 (P=0.027). For 57 pts with a CA COD, PMRs for myeloma (9.66), kidney CA (4.63), liver CA (4.36), NHL (4.13), and all leukemia (3.19) were significantly elevated (P<0.01). Conversely, the PMR for lung CA was 0.32 (P=0.002). There was 1 death from breast CA and none from gynecological CA. PMR for colorectal, pancreatic and prostate CA were not divergent from expected. Compared to the control population, the age distribution of deaths was identical for heart disease, septicemia, and suicide. Age at death was not younger than expected in pts with myeloma but there was a tendency for death at a younger age for GD pts with NHL, chronic liver disease and Parkinsonism. COD significantly more prevalent in surgically asplenic pts included chronic liver disease, septicemia, GI bleeding, PHT and post-splenectomy complications. Spleen status was statistically irrelevant to CA deaths including myeloma except for hepatocellular CA (splenectomy) and CLL (intact spleen). Conclusions: With earlier diagnosis, improved risk assessment and phase-out of splenectomy, COD that we encountered (chronic liver disease, GI bleeding, septicemia, PHT, suicide and drug dependency) should be increasingly rare with timely institution of appropriate treatment. Our study population of untreated pts (estimated at 5% of all US GD1 deaths from 1950–2008 but a substantially greater percentage of GD1 deaths over age 60y), should serve as a valuable control for future studies of the effect of GD1 treatment on mortality due to malignancy or other later course events. Disclosures: Weinreb: Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire HGT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Actelion Corporation: Speakers Bureau.

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Stein, Brady L., Ahmad Naim, Michael R. Grunwald, Alison R. Moliterno, Stephen T. Oh, Dilan Paranagama, Joseph A. Cordaro, et al. "Examining the Clinical Features and Underlying Cardiovascular Risk Among Patients with Polycythemia Vera in the REVEAL Study." Blood 128, no. 22 (December 2, 2016): 1934. http://dx.doi.org/10.1182/blood.v128.22.1934.1934.

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Abstract Background:Patients with polycythemia vera (PV) often present with a broad range of clinical characteristics that may contribute to increased risks of cardiovascular (CV) morbidity and mortality, including thrombotic events (TE). Limited contemporary real-world data have been reported about the clinical burden of PV and treatment patterns in the United States. The ongoing REVEAL study collects data on disease burden, clinical management, patient-reported outcomes, and healthcare resource utilization for patients with PV in the United States. This analysis reports clinical characteristics, including underlying CV risk factors, for patients enrolled in the REVEAL study as of April 28, 2016. Methods: REVEAL is a multicenter, nonrandomized, prospective, observational study enrolling patients ≥18 years of age with a PV diagnosis who are actively managed in an academic or community setting. For this analysis, data regarding PV disease and diagnosis, clinical characteristics, and treatment patterns were collected at enrollment during usual-care visits and were based on physician assessment, electronic medical records, and local laboratory values. Ten-year CV risk factors selected for this analysis were adapted from the Framingham Heart Study for CV diseases. Results: At data cutoff, 2307 patients were available for this analysis. Mean (SD) age was 66.3 (12.2) years, 54.4% were male, 89.9% were white, 62.7% had at least some college education, and 51.1% were retired. Approximately 6% of patients had a family history of PV, primarily in parents (35.1%) and siblings (33.8%). A history of second malignancies was reported for 344 patients (14.9%). The majority of patients (84.6%) were diagnosed with PV based on an abnormal blood test alone or in combination with a bone marrow test. Among patients who were diagnosed with a mutational test (n=1078), 95.2% were diagnosed via an abnormal JAK2V617F test result. Abnormal hemoglobin (57.3%), hematocrit (55.4%), or both (47.5%) were among the most common blood values assessed for PV diagnosis. At diagnosis, 58.5% of patients were classified with high-risk PV (age ≥60 years or history of a TE); this percentage increased to 77.3% at REVEAL enrollment. The average (SD) disease duration from diagnosis to enrollment was 5.8 (6.1) years. At enrollment, 91.5% of patients were under active management for PV (phlebotomy ± aspirin, 34.0%; hydroxyurea ± aspirin, 27.0%; and phlebotomy + hydroxyurea ± aspirin, 23.2%). Underlying CV risk factors that were either diagnosed or treated in 86.0% of enrolled patients included hypertension (66.5%), history of smoking (46.2%), current smoking at enrollment (10.9%), obesity (34.2%), hyperlipidemia (27.4%), and diabetes (14.8%). At enrollment, 431 (18.7%) patients reported having ≥1 TE, including 181 patients who had a TE between PV diagnosis and enrollment. Venous and arterial TEs were reported in 11.1% and 8.6% of patients, respectively. Most commonly reported venous TEs were deep vein thrombosis (5.9%) and pulmonary embolism (2.5%); most common arterial TEs were cerebrovascular arterial thrombosis including transient ischemic attack (5.1%) and acute myocardial infarction (1.7%). Increased rates of TEs were observed among patients with hyperlipidemia (23.6%) and hypertension (21.0%; Table 1), compared with patients who did not have any risk factors (10.5%). Conclusion: A large proportion of patients in the REVEAL study had 1 or more underlying CV risks, including age, hypertension, smoking, obesity, hyperlipidemia, and diabetes, which may contribute to the risk of thrombosis. Longitudinal data from REVEAL will provide a better understanding of how these factors affect CV outcomes over time. Disclosures Stein: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Naim:Incyte Corporation: Employment, Equity Ownership. Grunwald:Janssen: Research Funding; Forma Therapeutics: Research Funding; Medtronic: Equity Ownership; Alexion: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Oh:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; CTI: Research Funding. Paranagama:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Boccia:Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Gilead: Speakers Bureau; Genentech: Consultancy, Honoraria, Speakers Bureau; Eisai: Consultancy, Honoraria, Speakers Bureau. Mesa:Ariad: Consultancy; CTI: Research Funding; Gilead: Research Funding; Galena: Consultancy; Novartis: Consultancy; Promedior: Research Funding; Celgene: Research Funding; Incyte Corporation: Research Funding.

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Guru Murthy, Guru Subramanian, Binod Dhakal, Vijaya R. Bhatt, Paulette Mehta, Patrick C. Foy, Laura C. Michaelis, Karen B. Carlson, and Ehab Atallah. "Incidence and Overall Survival of Therapy Related Myeloid Neoplasm in United States." Blood 128, no. 22 (December 2, 2016): 3992. http://dx.doi.org/10.1182/blood.v128.22.3992.3992.

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Abstract Background: Therapy related myeloid neoplasm (t-MN) such as acute myeloid leukemia and myelodysplasia are emerging challenges in the current era when newer therapies are improving patient survival in many malignancies. Although clinical trials have reported the outcomes of t-MN, the real world data on its incidence and overall survival (OS) at population level remains sparse. Methods: Using Surveillance Epidemiology and End Results (SEER-18) database, we identified patients aged ≥ 10 years with pathologically confirmed t-MN (ICD-0-3 code 9920) diagnosed between the years 2000-2013 and actively followed. Incidence rate per 100000 population and incidence rate ratio (IRR) were calculated to describe the relative differences in disease incidence between the subgroups. Race was divided as Whites, Blacks, American Indians and Asian/pacific islanders. Three year OS was calculated by Kaplan-Meier method and compared by log rank test. Determinants of OS were analyzed with Cox proportional hazard regression method. Statistical analyses were done with significance level of p < 0.05. Results: A total of 941 patients with t-MN who met the study criteria were identified. Median age of the cohort was 63 years (10-85 years). Majority of the patients had age ≥60 years (58.2%), females (55.2%) and White race (86.4%). Overall incidence of t-MN was 0.09 cases/100000 population and showed significant variations with age, race and the period of diagnosis (Table 1). The disease incidence increased significantly after the age 40 (IRR ranging from 4.23 to 15.68, p < 0.01) and after the year 2005 (IRR ranging from 2.97 to 10.42, p < 0.01). Compared to White race, Blacks (IRR 0.65, p < 0.01) and Asian/pacific islanders (IRR 0.55, p < 0.01) had a significantly lower disease incidence. The 3-year OS significantly declined with increasing age (41.8% in age group 10-39, 27.3% in age group 41-59, 11.9% in age group 61-79 and 8.0% in age ≥ 80, p < 0.01). However, 3-year OS did not significantly vary by gender (19.3% in females vs. 20.7% in males, p = 0.92) or race (Whites 19.9%, Blacks 10.6%, American Indians 26.7%, Asian/pacific islander 30.7%, p = 0.43). There was an improvement in the 3-year OS over period (year 2000-2004- 13.4% vs. year 2005-2009 -17.1% vs. year 2010-2013 - 20.6%, p < 0.01). On multivariate analysis, increasing age was associated with significantly higher risk of mortality (age 40-59 - HR 1.46, CI 1.07 - 2.00, p = 0.01; age 60-79 - HR 2.32, CI 1.72 - 3.14, p < 0.01; age ≥80 - HR 3.81, CI 2.63 - 5.50, p < 0.01). Compared to the period 2000-2004, a significantly lower risk for mortality was seen in the period 2010-2013 (HR 0.55, CI 0.42-0.74, p < 0.01). Conclusions: The incidence of t-MN has significantly increased in the last decade and varies with factors such as age and race. Although OS has improved in the period 2010-2013, outcomes of this disorder continue to remain poor at the population level. Further research to identify the disease risk factors and development novel therapies is required to improve the outcomes. Disclosures Michaelis: Pfizer: Equity Ownership; Cellgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria. Atallah:Pfizer: Other: Grant review; Takeda: Research Funding; Novartis: Consultancy; BMS: Consultancy; CTI biopharma: Consultancy; Incyte: Consultancy; Ariad: Honoraria.

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Mato, Anthony R., Nicole Lamanna, Chaitra S. Ujjani, Danielle M. Brander, Brian T. Hill, Christina Howlett, Alan P. Skarbnik, et al. "Toxicities and Outcomes of Ibrutinib-Treated Patients in the United States: Large Retrospective Analysis of 621 Real World Patients." Blood 128, no. 22 (December 2, 2016): 3222. http://dx.doi.org/10.1182/blood.v128.22.3222.3222.

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Abstract Introduction: Ibrutinib (Ibr) is a kinase inhibitor (KI) indicated for treating CLL. Clinical trials that led to its approval showed that its unique side effects differ from traditional chemotherapy toxicities. We previously reported (Mato et al, ASH 2015) that intolerance was the most common reason for discontinuation of Ibr in 123 patients treated in a real world setting. Whether reasons for discontinuation reported in clinical trials mirror those encountered in the real world is unknown and has not been studied. Therefore, we conducted a retrospective analysis of 621 CLL patients treated with Ibr either on clinical studies or commercially. We aimed to compare the type and frequency of toxicities reported in either setting, assess discontinuation rates, and evaluate outcomes. Patients and Methods: This multicenter, retrospective analysis included Ibr-treated CLL patients at 9 US cancer centers or the Connect® CLL Registry. We examined demographics, dosing, discontinuation rates and reasons, toxicities, and outcomes. The primary endpoint was progression-free survival (PFS) (time from KI treatment to progression, death or last f/u) as determined by the Kaplan Meier method. Comparisons of outcomes data were made using the log rank (LR) test. All other comparisons were descriptive. Results: 621 patients treated with Ibr were identified. Table 1 includes available baseline characteristics stratified by line of therapy. A total of 546 (88%) patients were treated with commercial drug. Clinical trial patients were younger (median age 57 vs. 61 years), had a longer time from diagnosis to Ibr (median 85 vs. 72 months) and were more consistently initiated at 420 mg daily (100% vs. 89%). With a median f/u of 14.5 months, the Ibr discontinuation rate was estimated to be 42% (median time to Ibr discontinuation was 7 months). Reasons for discontinuation are listed in table 2. Notably, Ibr toxicity was the most common reason for discontinuation in all settings. Ibr starting dose (420 mg daily vs. < 420 mg daily) did not impact the proportion of patients who discontinued Ibr due to toxicity (51% vs. 50%). In relapsed CLL, the 5 most common Ibr-related toxicities as a reason for discontinuation included: atrial fibrillation (12.3%), infection (10.7%), pneumonitis (9.9%), bleeding (9%), and diarrhea (6.6%). In front line CLL, the 3 most common Ibr-related toxicities as a reason for discontinuation included arthralgia (41.6%), atrial fibrillation (25%), and rash (16.7%). Median times to discontinuation by toxicity were as follows: bleeding (8 months), diarrhea (7.5 months), atrial fibrillation (7 months), infection (6 months), arthralgia (5 months), pneumonitis (4.5 months), and rash (3.5 months). Median PFS and OS for the entire cohort were 35 months and not reached (median f/u 17 months) respectively. Figure 1 describes PFS for Ibr treated patients stratified by line of therapy (A), reason for discontinuation (B), clinical trial participation (C) and depth of response (D). In a multivariable model, complex karyotype was validated as an independent predictor of PFS (HR 1.6, CI 1.1-2.5 p=.04) but not OS (HR 1.6, CI .9-3.1 p=.1). Conclusions: In the largest reported series on Ibr-treated CLL patients, we show that 40% of patients have discontinued Ibr during this observation period. Intolerance as opposed to CLL progression or transformation was the most common reason for discontinuation. As compared to previous reports from clinical trials, the discontinuation rate appears to be higher suggesting (1) a learning curve in terms of toxicity management, (2) a higher incidence of toxicity in clinical practice, (3) or a lower threshold for discontinuation given alternative choices. Outcomes remain excellent and were not impacted by line of therapy and whether patients were treated on studies or commercially. These data strongly argue to find strategies to minimize Ibr intolerance so that efficacy can be further maximized. Figure 1 Figure 1. Disclosures Mato: Abbvie, Acerta Pharma, Gilead Sciences, ProNAi, TG Therapeutics, Theradex: Research Funding; Abbvie, Gilead Sciences, Pharmacyclics, TG Therapeutics: Consultancy. Lamanna:Acerta: Research Funding; TGR Therapeutics: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria, Research Funding; Roche-Genentech: Honoraria, Research Funding; Celgene: Honoraria; AbbVie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Infinity: Research Funding; Acerta: Research Funding; TGR Therapeutics: Research Funding. Ujjani:Gilead: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Pharmacyclics: Consultancy. Brander:TG Therapeutics: Research Funding; Gilead: Honoraria. Howlett:Sandoz: Honoraria; Teva: Speakers Bureau; Amgen: Honoraria; Pfizer: Honoraria; Eisai: Honoraria. Skarbnik:Gilead Sciences: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genentech: Speakers Bureau; Abbvie: Consultancy; Pharmacyclics: Consultancy. Cheson:Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kiselev:Celgene: Employment, Equity Ownership. Nasta:Millennium Pharmaceuticals: Research Funding. Schuster:Janssen Research & Development: Research Funding; Hoffman-LaRoche: Research Funding; Gilead: Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding. Porter:Novartis: Patents & Royalties, Research Funding; Genentech: Employment. Nabhan:Seattle Genetics: Research Funding; Cardinal Health: Consultancy; Infinity: Consultancy; Abbvie: Consultancy; Genentech: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; Astellas: Research Funding. Barr:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy.

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POSNER, RICHARD A. "From the new institutional economics to organization economics: with applications to corporate governance, government agencies, and legal institutions." Journal of Institutional Economics 6, no. 1 (January 25, 2010): 1–37. http://dx.doi.org/10.1017/s1744137409990270.

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Abstract:This paper applies the principles of organization economics (an offshoot of organization theory and a cousin of the New Institutional Economics) to a variety of organizations, mainly public ones. Organization economics seeks to understand and improve the ways in which organizations overcome agency costs, information costs, and other obstacles to efficiency. The private organization discussed in the paper is the modern publicly held (that is, dispersed ownership) business corporation, and the particular problem on which I focus is excessive executive compensation as a symptom of weaknesses in corporate governance. I then discuss two public organizations involved in national security – the US intelligence ‘community’ (a kind of mega-organization) and the Federal Bureau of Investigation in its role as the nation's principal domestic intelligence service. Both exhibit significant dysfunction that organization economics can help us to understand and overcome. I then discuss two types of public organization that have been more successful in overcoming obstacles to organizational efficiency: the judiciary of common law nations, such as the United States, and the very differently structured judiciary of civil law nations, such as France, Germany, and Japan.

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Jayakrishnan, Thejus, Yazan Samhouri, Veli Bakalov, Zena Chahine, Rodney E. Wegner, Cyrus Khan, Salman Fazal, and John Lister. "Predictors and Long Term Outcomes for DLBCL Patients Undergoing Surgery Prior to Systemic Therapy." Blood 136, Supplement 1 (November 5, 2020): 11. http://dx.doi.org/10.1182/blood-2020-137827.

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Background Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 22% of newly diagnosed non-Hodgkin's lymphoma per year in the United States. Combination chemoimmunotherapy with or without radiation therapy is recommended for the upfront treatment of DLBCL (Yang Liu, AJH,2019). A minority of patients undergo surgery prior to the initiation of systemic therapy for symptom relief or treatment of complications related to the disease. There are concerns on the delay in initiation of systemic therapy when surgery is performed and the potential impact on long term survival in this aggressive chemosensitive disease. We aimed to explore the characteristics of patients undergoing surgery prior to systemic therapy (sxfirst), the predictors for sxfirst and the survival outcomes. Methods We queried the National Cancer Database for patients with DLBCL (ICD-0-3 code 9680) diagnosed from 2006-2015. Inclusion criteria were patients that received systemic therapy as first-line course of treatment and excluded patients with incomplete or missing data for disease stage, treatment characteristics and follow-up. We also excluded patients who underwent biopsy procedures for diagnosis and local procedures such as tumor destruction or ablation. Subgroup analysis of patients that received sxfirst was performed. Time-to-initial therapy (TTI) was defined as time in days (d) from diagnosis to systemic therapy. Survival was measured in terms of months (m) from the day of diagnosis. Stepwise multivariate logistic regression analysis for predictors of sxfirst and propensity score adjusted survival analysis was performed. Results Of 208,748 patients with DLBCL, 138,096 patients met the inclusion criteria of whom 6,381 (4.6%) were sxfirst. The characteristics of sxfirst are summarized in Table 1. Median age was 66 (interquartile range IQR 55-75) years and 61.1% were males. Majority were non-Hispanic whites, had private or medicare insurance, had comorbidity score of 0 and stage I disease. Most patients were treated in comprehensive community cancer centers. The top 5 extra-nodal disease sites were gastrointestinal (26.2%), male reproductive system (16.4%), brain and spinal cord (6.4%), endocrine system (4.1%) and head and neck (3.0%). The median follow up was 47.6 (IQR 14.0-78.9) months. The predictors for sxfirst are described in Table 2. The following disease sites were associated with higher likelihood of sxfirst: male reproductive system (p-value<0.005), gastrointestinal system (p-value<0.005), endocrine system (p-value<0.005), brain and spinal cord (p-value=0.01) and head and neck (p-value=0.02) while the following factors were associated with lower likelihood of sxfirst - medicaid insurance (p-value=0.01), comorbidity score >=3 (p-value 0.007), more recent year of diagnosis, advanced stages of disease and presence of B-symptoms. The TTI for systemic therapy was delayed in sxfirst group - 34 (IQR 22-51) days vs. 21 (IQR 11-35) days, p-value<0.005. The 5-year overall survival for the sxfirst group was 64% (95% CI 62-65%) vs. 57% (95% CI 56-57%)- HR 0.75 (95% CI 0.71 - 0.81). The factors associated with increased mortality were advanced age, higher comorbidity score, lower educational status, advanced clinical stage of the disease, presence of B-symptoms , disease primarily located in the bone, brain and spinal cord. Conclusion The findings of the present study are twofold. First, the present study describes the characteristics and predictors of sxfirst among DLBCL patients. Second, if surgery is absolutely necessary prior to systemically treating DLBCL, the study suggests that the delay does not seem to impact long term survival of these patients and is similar to the 5-year overall survival (64%) reported for DLBCL when all stages and treatment strategies are combined (seer.cancer.gov/statfacts/dlbcl). While there are unmeasured confounding factors as a result of the absence of adequate prognostic markers and treatment characteristics in the database, it is possible that surgery truly doesn't impact the survival outcomes significantly. Further evaluation of this practical question is warranted in large scale prospective studies. Disclosures Khan: Abbvie: Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Beigene: Honoraria; Seattle Genetics: Honoraria. Fazal:Stemline: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; Karyopham: Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Soror, Noha N., Ashleigh Keiter, Qiuhong Zhao, Julianna Roddy, Sam Penza, Jonathan E. Brammer, Yvonne A. Efebera, et al. "Survival Implications of Opioid Use after Blood and Marrow Transplantation." Blood 136, Supplement 1 (November 5, 2020): 2–3. http://dx.doi.org/10.1182/blood-2020-134463.

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B ackground Premature death from opioid-related causes imposes an enormous public health burden across the United States. Between 2001 and 2016, the number of opioid-related deaths in the United States increased by 345%, from 9489 to 42 245 deaths (33.3 to 130.7 deaths per million population. Moreover, opioids may have immunosuppressive properties independent of their psychotropic effects; opioid use has been associated with increased invasive pneumococcal disease in a nested case-control study of 1233 Medicaid patients from Tennessee. In liver transplant recipients, opioid use disorder has been associated with increased mortality after transplant. The impact of opioid use disorder on patients receiving blood and marrow transplant (BMT) remains to be defined. Methods We performed a retrospective analysis of all consecutive adult patients who had BMT (autologous and allogeneic) from 1/1/2008 through 1/1/2018 at the James Comprehensive Cancer Center. Overall survival (OS) was measured from the date of transplant to the date of death, censoring at date of last follow up if alive. Progression free survival (PFS) was measured from the date of transplant to the date of disease progression or the date of death, whichever occurred first, censoring at last follow up if no event. OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Opioid use (OU) was defined as a binary yes/no variable if an opioid was prescribed upon discharge from the hospital after BMT. The impact of OU, along with other patient, disease, and BMT related factors, on PFS/OS, was analyzed using Cox regression method. Results A total of 1585 patients were included in the analysis (Table 1). The median age at BMT was 58 (range=18-79) years; 59% were males; 60% had autologous transplants; and 58% were prescribed opioids upon discharge from the hospital. OU was significantly more in patients who were younger, have had allogeneic transplant, reduced intensity conditioning, had acute myeloid leukemia (AML), or higher BMT comorbidity index (CMI). On univariable analysis, OU was not associated with cumulative incidence of relapse (CIR) or PFS however it was associated with inferior OS; hazard ratio (HR)=1.25, 95% CI: 1.06-1.49; p=0.01 (Figure-1). There were no differences in CIR, PFS, or OS when autologous and allogeneic transplants were analyzed separately. Upon multivariable analysis of OS, OU lost statistical significance after controlling for age, diagnosis, type of transplant, intensity of conditioning regimen, CMI, and disease risk index (DRE). Of interest, OU independently predicted for superior OS at 100 days and 365 days post-BMT; HR=0.29, 95% CI 0.16-0.50 (p=<.0001) and HR=0.47, 95% CI 0.32-0.69 (p<0.001); respectively. Conclusion: Our results suggest that opioid use (OU) may have a long term negative impact on survival in BMT patients. The apparently protective effects of OU early on after BMT is elusive but may be possibly related immunomodulatory effects of opioids. A major limitation of our study is that OU is analyzed at a single time point at hospital discharge after BMT. We plan to undertake a more detailed analysis of ongoing OU after discharge and its impact on survival outcomes after BMT. Disclosures Brammer: Celgene Corporation: Research Funding; Seattle Genetics, Inc.: Speakers Bureau. Efebera:Celgene: Research Funding; Ohio State University: Current Employment; Pharmacyclics: Research Funding; Takeda: Honoraria, Speakers Bureau. Mims:Abbvie: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau. Chaudhry:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Jaglowski:Novartis: Consultancy, Research Funding; CRISPR: Consultancy; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. William:Kyowa Kirin: Consultancy, Honoraria; Merck: Research Funding; Seattle Genetics: Research Funding; Incyte: Research Funding; Guidepoint Global: Consultancy; Dova: Research Funding; Celgene: Consultancy, Honoraria.

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Verstovsek, Srdan, Jingbo Yu, Jonathan K. Kish, Dilan Chamikara Paranagama, Jill Kaufman, Jessica Chung, Michael R. Grunwald, Philomena Colucci, and Ruben A. Mesa. "Real-World Risk Assessment and Treatment of Patients with Myelofibrosis at Community Oncology Practices in the United States." Blood 132, Supplement 1 (November 29, 2018): 1765. http://dx.doi.org/10.1182/blood-2018-99-115294.

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Abstract Introduction Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by marrow fibrosis, extramedullary hematopoiesis, and leukoerythroblastosis. Clinical manifestations include severe anemia, splenomegaly, and symptoms. Median survival in patients with primary MF ranges from 2 to 11 years, depending on risk categorization. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines recommend the International Prognostic Scoring System (IPSS) for risk stratification at diagnosis; other systems including the Dynamic IPSS (DIPSS) and the DIPSS-Plus are also cited in the Guidelines. Treatment recommendations are risk-adapted in the NCCN Guidelines. The objective of this study is to describe how patients are risk stratified at diagnosis by community hematologists/oncologists and the impact that risk stratification has on the initiation of MF-directed treatments. Methods Medical chart reviews were conducted at community hematology/oncology practices in the OPEN network. Adult patients diagnosed with primary MF, post-PV MF, or post-ET MF between 1/2012 and 12/2016 and receiving care for at least 6 months were included. Data were collected with an electronic case report form (eCRF) with questions on clinical characteristics (symptoms, Hgb, WBC, blast %, and PLT) and risk assessment method used at diagnosis (IPSS, DIPSS, or DIPSS-Plus), treatments, and outcomes. A data-derived IPSS risk score was calculated for each patient. To assess the accuracy of the assigned risk, a data-derived risk score, corresponding to the system used by the provider, was also calculated. Patients were classified as treated at diagnosis if they received MF-directed therapy (hydroxyurea, interferon, ruxolitinib, or clinical trial) or allogeneic hematopoietic cell transplant (HCT) within 120 days of diagnosis. The methods and rates of risk stratification, accuracy of the provider-assigned risk versus data-derived risk, and treatment administered were reported. Results A total of 338 patients with MF from 28 community hematology/oncology practices were included. Mean (SD) age at diagnosis was 65.3 (11.8) years, 51.8% were male, and 68.3% had primary MF. JAK2, MPL, and CALR mutations were tested in 86.1%, 70.1%, and 60.9% of patients at diagnosis, of these, 71.1%, 23.2%, and 14.6% were positive, respectively; 18.4% (38/206) were triple negative. Median follow-up from diagnosis was 27.5 months (IQR, 18.5-42.6). Approximately 32% of patients did not have a risk classification in their medical records at diagnosis. A scoring system was used for risk assignment in 45.3% of patients; DIPSS (23.0%) and IPSS (21.3%) were most commonly used. Of all 338 patients, the corresponding data-derived risk classifications were: 5.6% low, 20.1% int-1, 18.3% int-2, and 55.9% high risk. Among those patients who were not assigned risk by their treating physicians (n=108), most had int-1 (28.7%), int-2 (17.6%), or high risk (43.5%) disease based on the data-derived IPSS risk classification. Of those who received a risk classification from their treating physician, 47.4% (n=109) received an inaccurate risk classification; among these patients, the risk was under-estimated for most (82.6%) (Table 1). Overall, 55.8% of patients (63.2% low-risk, 55.9% int-1, 52.5% int-2, 56.1% high-risk) received MF-directed pharmacological treatment or HCT within 4 months of diagnosis. Among all patients receiving MF-directed treatment, the mean time from diagnosis to treatment initiation was 5.3 months (SD=1.8), and the most common first pharmacological treatments were ruxolitinib (49.8%) and hydroxyurea (46.7%). Splenomegaly (81.3%), symptoms (72.6%), and anemia (65.6%) were top cited indications for treatment initiation. The treatment initiation rate was higher among those patients correctly risk classified compared to those incorrectly classified (64.2% versus 49.5%, p=0.032). Conclusions Nearly one-third of patients with MF did not receive a risk classification at diagnosis. When risk was assigned, almost half were incorrectly classified. Just over half of patients received treatment within four months of diagnosis. Patients who were correctly risk classified at diagnosis were more likely to start treatment promptly upon diagnosis versus those incorrectly risk classified, which may be attributable to the under-estimation of risk. Disclosures Verstovsek: Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees. Yu:Incyte Corporation: Employment, Equity Ownership. Kish:Cardinal Health: Employment. Paranagama:Incyte: Employment, Equity Ownership. Kaufman:Cardinal Health: Employment. Chung:Cardinal Health: Employment. Grunwald:Genentech: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Alexion: 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; Medtronic: Equity Ownership; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding. Colucci:Incyte: Employment, Equity Ownership. Mesa:UT Health San Antonio - Mays Cancer Center: Employment; NS Pharma: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Novartis: Consultancy; Pfizer: Research Funding.

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Pashos, Chris L., Brian G. M. Durie, Robert M. Rifkin, Jatin J. Shah, Thomas K. Street, Kristen A. Sullivan, and Zeba M. Khan. "Variation In Health-Related Quality of Life (HRQOL) by ISS Stage and ECOG Status Among Multiple Myeloma Patients." Blood 116, no. 21 (November 19, 2010): 3828. http://dx.doi.org/10.1182/blood.v116.21.3828.3828.

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Abstract Abstract 3828 Introduction: Attention is being paid to HRQOL when monitoring hematologic disorders or the impact of treatments on those disorders. Minimal HRQOL data have been published on multiple myeloma (MM) patients (pts) in the United States (US). This analysis characterizes variation in the HRQOL of pts with active, symptomatic MM by International Staging System (ISS) stage and ECOG status. Methods: Data were collected as part of Connect MM®, a prospective observational registry initiated in September 2009 involving centers in the US. Data on pt demographics and clinical characteristics were provided by clinicians. HRQOL was reported by pts in the clinic at enrollment, within two months of diagnosis. Pts completed 3 psychometrically validated instruments: EQ-5D, Brief Pain Inventory (BPI), and Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM). Standard analyses were conducted of each instrument given clinical characteristics at that time. Reported mean BPI, EQ-5D and FACT-MM scores were analyzed by ISS and ECOG status. Statistical significance of score differences among sub-cohorts was ascertained by ANOVA using SAS 9.1. Results: HRQOL data were reported by 328 pts, enrolled from 135 centers. Pts were predominantly male (60%) and white (79%) with mean age at 67.3 (standard deviation [SD] 11.6) yrs. HRQOL scores by evaluable ISS stage (n=236) and ECOG status (n=258) are presented. BPI data (on a scale of 0 [no pain] to 10 [worst pain]) indicate that average reported pain worsens by ISS and ECOG severity. Mean EQ-5D scores (on a scale of 1 [no problem] to 2 [some problems] to 3 [incapacity]) indicate that pain/discomfort, and usual activities are most compromised, and with self care increase in severity as ISS and ECOG worsen. Anxiety/depression level is associated with ECOG, but not with ISS. FACT-MM results indicate that ISS and ECOG severity is associated with greater decrement in physical and functional domains. The associations of HRQOL with ECOG status were stronger than with ISS stage. Specifically, scores on the BPI, all EQ-5D domains, and all FACT-MM domains (except the social/family domain) were statistically significantly associated with more severe ECOG status. Conclusions: Initial results from the Connect MM® Registry indicate that HRQOL worsens with worsening ISS stage and ECOG status, especially in physical and functioning domains, pain/discomfort, and ability to conduct usual activities and to provide self care. These areas should receive attention at diagnosis. Future analyses should be conducted on: (1) more newly diagnosed patients; (2) how HRQOL may be affected over time with changes in disease; and, (3) how HRQOL may be influenced by alternative therapies. Results reported here should serve as useful baseline reference. Disclosures: Pashos: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: CONNECT is a disease registry and includes data on off-label use of anti-myeloma agents. Durie:Celgene & Millennium: Consultancy. Rifkin:Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Cephalon: Speakers Bureau; Dendreon: Speakers Bureau. Shah:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding. Street:Celgene: Employment. Sullivan:Celgene: Employment, Equity Ownership. Khan:Celgene Corporation: Employment.

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Copelan, Edward A., Jonathan M. Gerber, Saad Z. Usmani, Michael R. Grunwald, Nilanjan Ghosh, Omotayo O. Fasan, Manisha Bhutani, James T. Symanowski, Derek Raghavan, and Belinda R. Avalos. "Establishment of Subspecialized Care in Hematologic Malignancies and a Hematopoietic Cell Transplantation Program." Blood 128, no. 22 (December 2, 2016): 3580. http://dx.doi.org/10.1182/blood.v128.22.3580.3580.

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Abstract Introduction Access to appropriate healthcare close to home is a national and global problem with huge geographic variation in availability of subspecialized care and specific therapies, as illustrated by hematopoietic cell transplantation rates [Gratwohl, et al. Lancet Hematol, 2015]. Disease-specific physician specialization appears to improve outcomes in hematologic malignancies [Go, et al. Mayo Clin Proc, 2015]. Charlotte is the 2nd largest city in the Southeastern United States and 17th largest in the US, yet subspecialized care in hematologic malignancies including a leukemia unit and hematopoietic cell transplantation (HCT) program were non-existent 3 years ago. The closest HCT program was a 90-minute drive from Charlotte. Many patients lacked the resources or willingness to travel to a transplant center and died of potentially curable diseases. Establishment of a transplantation program, in particular, requires a substantial upfront investment, broad infrastructure and highly specialized interdisciplinary care. Better transplant outcomes have been associated with higher numbers of procedures [Loberiza, et al. Blood, 2005], but programs established over the last decade have struggled to attract adequate numbers of patients to support the required investment. Methods In 2011 Carolinas HealthCare System (CHS), which serves as a healthcare safety net for the region, decided to develop the Levine Cancer Institute as a primary through quaternary referral and treatment center, integrated through more than 12 sites, with a key focus being a program in HCT. The Department of Hematologic Malignancies and Blood Disorders was established in September 2012. We envisioned that the development of specialized care in leukemia, lymphoma, and plasma cell disorders, as well as more complex non-malignant hematologic disorders, would improve the quality of care for patients with those diseases, attract larger volumes of patients, and serve to identify patients appropriate for HCT in a timely manner. A 16 bed hematologic malignancies unit housed in a protected environment was constructed and completed in January 2014. Results Starting with 4 general hematologists, the department has grown over 4 years to include 23 faculty members, 14 of whom provide subspecialized care in hematologic malignancies and HCT. Patient volumes have grown more than six-fold during this time. The HCT Program performed its first transplant in March 2014, with a total of 60 transplants performed in 2014 and 81 in 2015. The HCT Program is on pace to perform over 100 transplants in 2016. The program received FACT accreditation in 2016, a little more than 2 years after the first HCT was performed. The age range of patients undergoing transplantation is from 22 to 76 (median 58) years. Sixty-nine percent of transplants have been autologous and 31% allogeneic, of which 65% were from haploidentical related donors. The proportion of transplants which are allogeneic is steadily increasing. More than 90% of patients who have undergone transplantation were referred through a disease-specific section. Non-relapse mortality (NRM) at 1 year is 1.8% for autologous transplants and 9.4% for allogeneic transplants, with survival rates at 1 year of 95.6% and 80.8% respectively. Notably, there is no difference in NRM (P=0.86), relapse-free survival (P=0.85), or overall survival (P=0.47) between HLA-identical and haploidentical transplant recipients. Conclusions Three years ago, for patients in Charlotte, access to subspecialized care in hematologic malignancies and HCT required significant travel. The development and growth of a program that provides disease-specific care in hematologic malignancies has overcome this barrier and has provided a base for growth of a newly established program in HCT. These developments have elevated the quality of care in hematologic malignancies in the Charlotte area and permit patients to receive appropriate and complex care close to home. Disclosures Gerber: Janssen: Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Usmani:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Novartis: Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Array: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Grunwald:Amgen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Medtronic: Equity Ownership; Janssen: Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees. Ghosh:Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SGN: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Research Funding; TG Therapeutics: Research Funding. Bhutani:Prothena: Research Funding; Takeda Oncology: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Symanowski:Endocyte: Consultancy; Eli Lilly & Co: Consultancy; Ra Pharma: Consultancy; Caris Life Sciences: Consultancy. Raghavan:Gerson Lehrman: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees. Avalos:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

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Stahl, Maximilian, Wei Wei, Pau Montesinos, Etienne Lengline, Rory M. Shallis, Judith Neukirchen, Vijaya R. Bhatt, et al. "Characteristics, Treatment Patterns and Outcomes Among Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Hyperleukocytosis: Findings from a Large International Patient Cohort." Blood 132, Supplement 1 (November 29, 2018): 4040. http://dx.doi.org/10.1182/blood-2018-99-112974.

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Abstract Introduction: Pts with AML often present with hyperleukocytosis, defined with a white blood cell count (WBC) of >50 or >100 × 109/L. Hyperleukocytosis is associated with higher rates of complications and death especially when associated with clinical leukostasis. There are no clear guidelines outlining the best cytoreductive strategy and the use of leukapheresis is based on institutional practice. Limited data is available regarding characteristics of AML pts with hyperleukocytosis, treatment patterns, short and long-term clinical outcomes. Methods: Data were collected retrospectively from 12 centers in the United States and Europe. Eligible pts had newly diagnosed AML, WBC > 50 × 109/L, and had received intensive chemotherapy (IC). Pts with hyperleukocytosis who did not receive IC are described in a separate abstract. Kaplan-Meier methods estimated overall survival (OS) from time of presentation till death or end of follow-up. Clinical evidence of leukostasis was defined as new onset hypoxia, chest pain, headache, focal neurological symptoms, priapism, intestinal ischemia and acute renal failure attributed to hyperleukocytosis by the primary provider of the pt. Results: Among 1050 pts with AML and hyperleukocytosis whose data were collected, 787 were reported to have received intensive chemotherapy and were included in this analysis. The median age was 55 years (range [R], 15-86), and 51% were male (Table 1). Median WBC at presentation was 109 × 109/L (R, 47-561) and 57% had WBC > 100 × 109/L. Median hemoglobin was 9.2 g/dL (R, 3.6-126) and median platelet count was 31 x 109/L (R, 3-1268). A good, intermediate and poor risk karyotype were present in 31%, 51% and 18% of pts, respectively. Clinical leukostasis, tumor lysis syndrome (TLS) and disseminated intravascular coagulation (DIC) were present in 27%, 28% and 18% of pts at time of presentation, respectively (Table 1). Organs affected by leukostasis were the lung, CNS, retina, heart, kidney and GI tract in 44%, 36%, 6%, 6%, 5% and 4%, respectively. Leukapheresis was administered in 117 pts (15%) (Figure 1). Four centers did not use leukapheresis. 31% of pts with clinical leukostasis underwent leukapheresis and 10% of pts without clinical leukostasis received leukapheresis (p<0.001). Pts, who underwent leukapheresis, had statistically significant higher WBC and higher % of FLT3 mutations compared to pts, who did not undergo leukapheresis (Table 1). In pts who did not receive leukapheresis, hyperleukocytosis was managed either by immediate initiation of intensive chemotherapy (n=342, 53%) or by the administration of hydroxyurea followed by intensive chemotherapy (n=302, 47%). Pts managed with leukapheresis, received either immediate (within 24h) induction of intense chemotherapy (n=71, 61%) or delayed (after 24h) induction of intensive chemotherapy (n=42, 36%) after completion of leukapheresis. The 30-day mortality was 16.6% (95%CI, 13.9-19.3%); 20%, 11% and 14% of pts were admitted to the ICU, underwent hemodialysis, or required mechanical ventilation, respectively (Table 2). After initiation of chemotherapy, 51% (95%CI, 46.9%-54.1%) had a complete remission (CR), 14% (95%CI, 11.4%- 16.4%) had a complete remission with incomplete count recovery (CRi) and 4% (95%CI, 2.5%-5.4%) achieved a partial remission (PR) whereas 32% (95%CI, 28.7%-35.4%) had no response to therapy (Table 2). Response to chemotherapy lasted a median of 202 days (R,14-3575) and 43% of pts experienced a relapse of their disease; 31% of pts underwent a hematopoietic stem cell transplant (HSCT). Median OS for all pts was 12.6 months (95%CI, 11.5-14.9) (Figure 1A). Median OS was 14.1 months (95%CI, 12.3-18.7) for pts with a WBC <100 × 109/L versus 11.5 months (95%CI, 9.3-14.1) for pts with a WBC >100 × 109/L (p=0.11) (Figure 1B). Median OS was 15.2 months (95%CI, 13.4-17.5) for pts without clinical leukostasis, significantly longer than the median OS of 7.4 months (95%CI, 3.9-9.8) for pts with symptoms of leukostasis (p<0.0001) (Figure 1C). Conclusions: To our knowledge, this is largest reported cohort of pts with AML and hyperleukocytosis treated with intensive chemotherapy. Clinical leukostasis was present in about a quarter of pts and was associated with worse OS. Most pts were managed with chemotherapy alone, and leukapheresis was only used in a small subgroup of pts (15%). The impact of leukapheresis and other variables on outcomes are presented in a separate abstract. Disclosures Montesinos: Novartis: Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Speakers Bureau. Bhatt:Pfizer: Consultancy; CSL Behring: Consultancy; Incyte: Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Fathi:Boston Biomedical: Consultancy, Honoraria; Jazz: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Astellas: Honoraria; Agios: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria. Khan:Teva: Speakers Bureau. Roboz:Janssen Pharmaceuticals: Consultancy; Aphivena Therapeutics: Consultancy; Roche/Genentech: Consultancy; Argenx: Consultancy; Aphivena Therapeutics: Consultancy; Jazz Pharmaceuticals: Consultancy; Sandoz: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy; Cellectis: Research Funding; Orsenix: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Cellectis: Research Funding; Sandoz: Consultancy; Otsuka: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; AbbVie: Consultancy; AbbVie: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Janssen Pharmaceuticals: Consultancy; Eisai: Consultancy; Otsuka: Consultancy; Daiichi Sankyo: Consultancy; Orsenix: Consultancy; Celltrion: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Eisai: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy. Cluzeau:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Speakers Bureau; Pfizer: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Consultancy; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Germing:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria. Mukherjee:Pfizer: Honoraria; Projects in Knowledge: Honoraria; BioPharm Communications: Consultancy; LEK Consulting: Consultancy, Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squib: Honoraria, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Aplastic Anemia & MDS International Foundation in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria. Brunner:Celgene: Consultancy, Research Funding; Takeda: Research Funding; Novartis: Research Funding. Ritchie:Incyte: Consultancy, Speakers Bureau; NS Pharma: Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau; Astellas Pharma: Research Funding; Bristol-Myers Squibb: Research Funding. Podoltsev:Pfizer: Research Funding; Sunesis Pharmaceuticals: Research Funding; LAM Therapeutics: Research Funding; Genentech: Research Funding; Boehringer Ingelheim: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; Celgene: Research Funding; Astellas Pharma: Research Funding; Celator: Research Funding; Daiichi Snakyo: Research Funding. Gore:Celgene: Consultancy, Research Funding. Zeidan:Otsuka: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria.

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Shallis, Rory M., Maximilian Stahl, Wei Wei, Pau Montesinos, Etienne Lengline, Judith Neukirchen, Vijaya R. Bhatt, et al. "Outcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database." Blood 132, Supplement 1 (November 29, 2018): 3999. http://dx.doi.org/10.1182/blood-2018-99-119755.

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Abstract Introduction: Hyperleukocytosis at time of acute myeloid leukemia (AML) diagnosis is associated with increased disease-related complications as well as early mortality. Many AML patients are not candidates for intensive chemotherapy (IC) because of disease-related or patient-specific factors. Limited data is available regarding the characteristics and outcomes of newly-diagnosed AML who present with hyperleukocytosis and do not receive IC. Methods: We retrospectively analyzed data from patients with newly-diagnosed AML and hyperleukocytosis (defined as white blood cell count [WBC] of 50 × 109/L or greater) who were reported not to have received IC at 12 major institutions in the United States, Spain, Germany and France from 1982 to the end of 2016. Collected variables included age, sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS), WBC, hemoglobin level, platelet count, renal and hepatic chemistry parameters, cytogenetic risk group, molecular abnormalities (if available), presence of tumor lysis syndrome (TLS), disseminated intravascular coagulation (DIC), clinical evidence of leukostasis, admission to an intensive care unit (ICU) at presentation, receipt of hydroxyurea, and administration of leukapheresis. Clinical evidence of leukostasis was defined as new onset hypoxia, chest pain, headache, focal neurological symptoms, priapism, intestinal ischemia and acute renal failure attributed to hyperleukocytosis by the primary provider of the patient. Kaplan-Meier analysis was used to estimate overall survival (OS) from time of presentation until death or end of follow-up. Patients with hyperleukocytosis who received IC are described in a separate abstract. Results: Of 1050 patients with AML and hyperleukocytosis reported to our dataset, 220 patients were reported not to have received IC and were included in this analysis. For those 220 patients, median age was 75 years, 57.7% were male, and most (62.8%) had an ECOG PS of 2 or greater. Median WBC, hemoglobin, and platelet count at presentation were 131.4 × 109/L (range [R], 50.4-620), 8.96 g/dL (R, 3.6-15.9), and 34 (R, 3-393), respectively; 61.5% presented with a WBC greater than 100 × 109/L. Cytogenetically-defined poor risk AML was diagnosed in 26.1% of patients. TLS, DIC or clinical leukostasis was present in 25.6%, 15.7%, and 32.5% of patients, respectively. Pulmonary, central nervous system, renal, cardiac, gastrointestinal, or retinal clinical evidence of leukostasis was present in 52.9%, 17.1%, 11.4%, 10%, 5.7% and 2.9%, respectively, of those with clinical leukostasis. The majority (72.9%) of patients received initial therapy with hydroxyurea with a median time from presentation to administration of 12 hours (R, 1-144). Only 15% of patients underwent leukapheresis. Commonly-used non-IC therapies included hypomethylating agents, clofarabine, low dose cytarabine, or best supportive care. The median OS of the entire cohort was only 22 (95%CI: 13-37) days. The 30-day mortality was 57.4%. The 60-day, 90-day, 180-day, and one-year OS probabilities were 37%, 31%, 20%, and 12%, respectively. Only 4.3% of patients proceeded to allogeneic stem cell transplant. Patients presenting with WBC >100 × 109/L (N=79) had a worse OS than those presenting with WBC <100 × 109/L (N=126), (median OS 0.4 [95%CI, 0.3-0.7] vs. 2 [95%CI, 1.2-3.5] months, respectively, p=0.02) and those with clinical evidence of leukostasis (N=50) had worse OS than those who did not (N=104), (median OS, 0.2 [95%CI, 0.1-0.8] vs 2.2 [95%CI, 1.3-3.5] months, respectively, p<0.0001) (Figure). Patients who underwent leukapheresis (N=31) did not have a significantly improved OS compared to those who did not undergo leukapheresis (N=175) with a median OS of 1.2 (95%CI, 0.2-12.4) vs. 0.7 (95%CI, 0.4-1.2) months, respectively (p=0.12) (Figure). The small number of patients undergoing leukapheresis limited assessment of impact of leukapheresis in multivariable analysis. Conclusions: We report the largest studied cohort of patients with newly-diagnosed AML presenting with hyperleukocytosis who did not receive IC. Outcomes were very poor with a median OS of 22 days and only 12% alive at one year. WBC >100K x 109/L and clinical leukostasis were associated with inferior survival, while leukapheresis did not seem to impact survival. Novel and effective therapies are urgently needed for this group of AML patients. Disclosures Montesinos: Daiichi Sankyo: Consultancy, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Bhatt:Incyte: Research Funding; CSL Behring: Consultancy; Pfizer: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Fathi:Agios: Honoraria, Research Funding; Astellas: Honoraria; Boston Biomedical: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Khan:Teva: Speakers Bureau. Roboz:AbbVie: Consultancy; Cellectis: Research Funding; Celltrion: Consultancy; Argenx: Consultancy; Aphivena Therapeutics: Consultancy; Eisai: Consultancy; Novartis: Consultancy; Otsuka: Consultancy; Astex Pharmaceuticals: Consultancy; Bayer: Consultancy; Celgene Corporation: Consultancy; Cellectis: Research Funding; Roche/Genentech: Consultancy; Roche/Genentech: Consultancy; Eisai: Consultancy; Aphivena Therapeutics: Consultancy; Otsuka: Consultancy; Pfizer: Consultancy; Sandoz: Consultancy; Sandoz: Consultancy; Orsenix: Consultancy; AbbVie: Consultancy; Janssen Pharmaceuticals: Consultancy; Astex Pharmaceuticals: Consultancy; Celltrion: Consultancy; Janssen Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Orsenix: Consultancy; Jazz Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Bayer: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Argenx: Consultancy. Cluzeau:Pfizer: Speakers Bureau; Sanofi: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Germing:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Novartis: Honoraria, Research Funding. Mukherjee:Takeda: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Projects in Knowledge: Honoraria; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; LEK Consulting: Consultancy, Honoraria; Bristol Myers Squib: Honoraria, Speakers Bureau; BioPharm Communications: Consultancy; Aplastic Anemia & MDS International Foundation in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria. Brunner:Celgene: Consultancy, Research Funding; Takeda: Research Funding; Novartis: Research Funding. Ritchie:NS Pharma: Research Funding; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; Bristol-Myers Squibb: Research Funding; ARIAD Pharmaceuticals: Speakers Bureau; Pfizer: Consultancy, Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau. Podoltsev:Astex Pharmaceuticals: Research Funding; Celator: Research Funding; Astellas Pharma: Research Funding; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Boehringer Ingelheim: Research Funding; CTI biopharma: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria. Gore:Celgene: Consultancy, Research Funding. Zeidan:Otsuka: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Agios: Consultancy, Honoraria.

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Keats, Jonathan J., Gil Speyer, Legendre Christophe, Christofferson Austin, Kristi Stephenson, Ahmet Kurdoglu, Megan Russell, et al. "Identification of Initiating Trunk Mutations and Distinct Molecular Subtypes: An Interim Analysis of the Mmrf Commpass Study." Blood 126, no. 23 (December 3, 2015): 722. http://dx.doi.org/10.1182/blood.v126.23.722.722.

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Abstract The Multiple Myeloma Research Foundation (MMRF) CoMMpass trial (NCT145429) is a longitudinal study of 1000 patients with newly-diagnosed multiple myeloma from clinical sites in the United States, Canada, Spain, and Italy. Each patient receives a treatment regimen containing a proteasome inhibitor, immunumodulatory agent, or both. Clinical parameters are collected at study enrollment and every three months through the five-year observation period. To identify molecular determinants of clinical outcome each baseline and progression tumor specimen is characterized using Whole Genome Sequencing, Exome Sequencing, and RNA sequencing. This will be the first public presentation of the interim analysis seven cohort with 760 enrolled patients of whom 565 are molecularly characterized. This cohort of patients includes 14 patients with baseline and secondary samples along with 7 patients with characterized tumor samples from the bone marrow and peripheral blood. Although the median follow-up time for the cohort is only 260 days the patients on proteasome and IMiD based combinations are currently showing a PFS and OS benefit compared to those receiving combinations with each agent alone. From the raw mutational analysis we identified 24 significant genes that are recurrently mutated and the mutated allele is detectably expressed in all but one, DNAH5. Suggesting these mutations are likely contributing to myelomagenesis through an unconventional mechanism. Interestingly, DIS3 mutations are independent of KRAS, NRAS, and BRAF indicating a potential mechanistic link while PRKD2 mutations are associated with t(4;14). To identify events driving the initiation of myeloma we performed a detailed clonality analysis using a bayesian clustering method that corrects for copy number abnormalities and tumor purity to assign mutations into distinct clonal branches versus the initiating trunk mutations. On average 63.8% of mutations are trunk mutations and in 86.7% of patients at least one trunk mutation is associated with somatic hypermutation of an immunoglobulin gene as expected in a late stage B-cell malignancy. This identified many expressed trunk mutations that did not come out in the classic significance analysis like ATM, EGR1, and CCND1. To identify molecular subtypes we performed unsupervised clustering using a consensus clustering approach on independent discovery and validation cohorts, which identified 12 distinct subtypes, using a combination of silhouette score and cumulative distribution of consensus scores. This analysis identified two distinct groups associated with t(4;14) with mutations in FGFR3 and DIS3 being exclusive to one subgroup. In addition, this analysis separates patients with cyclin D translocations into three different groups, with one group having the second lowest PFS proportion. Three patients without CCND1 or CCND3 translocations were found to have IgH translocations targeting CCND2. The MAF subgroup was associated with the lowest OS and PFS proportion, and the three MAF/MAFB translocation negative patients in the subgroup all had MAFA translocations. The remaining 6 subgroups are associated with hyperdiploid copy number profiles and harbor the majority of the IgH-MYC translocation events. Two of the hyperdiploid groups are associated with a low level of NFKB activation compared to the remaining four, one of these is defined by the highest proliferation index but paradoxically the other has the second worst OS proportion. Another group is enriched with FAM46C and NRAS mutations. The genomic profiles of the paired tumors isolated from the peripheral blood and bone marrow are highly similar indicating these are not genetically distinct tumor compartments, at least in this subset of seven patients. Applying our bayesian clustering method to the serial samples resolved additional clonal clusters as mutations with similar cancer cell fractions at diagnosis clearly diverged at later timepoints. These analyses have identified tumor initiating mutations and new subtypes of myeloma, which are associated with distinct molecular events and clinical outcomes. Disclosures Jagannath: Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Merck: Honoraria; Janssen: Honoraria. Siegel:Celgene Corporation: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Merck: Speakers Bureau. Vij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy. Zimmerman:Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Onyx: Honoraria. Niesvizky:Celgene: Consultancy, Speakers Bureau. Rifkin:Onyx Pharmaceuticals: 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; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

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21

Merryman, Reid W., Luca Castagna, Paolo Corradini, Vincent T. Ho, David A. Bond, Samantha Jaglowski, Michael A. Spinner, et al. "Safety and Efficacy of Allogeneic Hematopoietic Stem Cell Transplant after Programmed Cell Death 1 (PD-1) / Programmed Cell Death Ligand 1 (PD-L1) Blockade for Classical Hodgkin Lymphoma: Analysis of a Large International Cohort." Blood 134, Supplement_1 (November 13, 2019): 775. http://dx.doi.org/10.1182/blood-2019-125039.

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Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have suggested that alloHSCT after PD-1 mAbs may be associated with severe immune-related complications including acute graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytokine release/febrile non-infectious syndrome (CRS). Prior studies of alloHSCT after PD-1 blockade in cHL have been limited by the small number of pts and short follow-up, preventing an accurate assessment of long-term outcomes and complications, risk factors for early toxicity, and the impact of transplant strategies such as choice of GVHD prophylaxis. We therefore assembled a large retrospective international cohort of cHL pts who underwent alloHSCT after PD-(L)1 blockade to better answer these questions, including an assessment of the impact of post-transplant cyclophosphamide (PTCy) on efficacy and toxicity. Methods: Medical records and databases were reviewed at 26 European and United States transplant centers to identify pts with cHL who underwent an alloHSCT any time after receiving a PD-1 or PD-L1 mAb. Response assessment was performed by local investigators according to Lugano 2014 criteria. Overall survival (OS), progression-free survival (PFS), cumulative incidence (CumInc) of relapse (CIR), non-relapse mortality (NRM), acute (a) and chronic (c) GVHD were estimated, as was the association between baseline variables and these outcomes. Results: Between 2014 and 2019, 150 pts were identified who underwent alloHSCT after a median of 10 (range, 1-74) doses of nivolumab (n=118), pembrolizumab (n=31), or avelumab (n=1). The median age was 31 (range 17-68) and pts had received a median of 4 (range, 2-11) lines of therapy prior to PD-(L)1 blockade. 138 pts (92%) had failed BV and 111 (74%) autologous HSCT. The best overall response to PD-(L)1 mAbs was CR for 62 pts (41%), PR for 55 (37%), SD for 17 (11%), PD for 15 (10%) and unknown for 1 (1%). Median time from last dose of PD-(L)1 mAb to alloHSCT was 80 days (range, 17-756) with 70 pts (47%) receiving intervening systemic therapy. At alloHSCT, 90 pts were in CR (60%), 45 in PR (30%), 5 in SD (3%), and 10 in PD (7%). Donors were haploidentical (n=71, 47%), matched sibling (n=29, 19%), matched unrelated (n=39, 26%), mismatched unrelated (n=7, 5%), cord blood (n=2, 1%), or unknown (n=2, 1%). Stem cell source was bone marrow (n=38, 25%), peripheral blood (n=110, 73%), or cord blood (n=2, 1%). GVHD prophylaxis included PTCy in 88 pts (59%) (69/71 (97%) with haploidentical donors; 19/79 (24%) with other donors). With a median post-alloHSCT follow-up for survivors of 23.8 months (range, 1-67), the 2y OS and PFS were 79% (95CI 71-86%) and 65% (95CI 55-73%), respectively, while the 2y CumIncs of relapse and NRM were 21% (95CI 13-29%) and 14%, (95CI, 8-22%), respectively (Fig. 1A-B). 27 pts have died, 3 due to disease and 24 to NRM, including aGVHD (n=7) and VOD (n=2). Veno-occlusive disease (VOD) occurred in 5 pts (day 100 CumInc 4%) and 29 pts (19%) developed CRS (grade 1 n=16; grade 2 n=7; grade 3 n=4; grade 4 n=2). The 6-month CumIncs of grade 2-4, grade 3-4 and grade 4 aGVHD were 39%, 16% and 8%, respectively. Hyperacute GVHD (onset ≤ 14 days after alloHSCT) occurred in 4% of pts and was fatal in 2 pts. The 2y CumInc of cGVHD was 45%. Neither receipt of > 10 doses (median) of anti-PD-(L)1 mAb nor undergoing alloHSCT ≤80 days (median) after last dose of PD-(L)1 mAb were associated with PFS or OS. However, pts with a shorter time to transplant (≤80 days) appeared to have a higher risk of severe (grade 3-4) aGVHD (6m CumInc 24% vs 9%, p=0.006). Recipients of PTCy in this cohort had lower 2y CumIncs of cGVHD (34% vs 58%, p=0.01) and relapse (12% vs 31%, p=0.02), superior 2y PFS (76% vs 54%, p=0.015), and similar rates of severe aGVHD (15% vs 18%, p=0.5), 2y NRM (12% vs 16%, p=0.5), and 2y OS (82% vs 78%, p=0.6). Conclusions: With extended follow-up of a large international cohort, our results argue that alloSCT performed after PD-(L)1 mAbs is a feasible strategy associated with an excellent PFS and a very low CIR for this disease. The use of PT-Cy appears to be associated with improved outcomes and may at present represent the optimal transplant strategy in this pt population. Figure Disclosures Corradini: kite: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Unum Therapeutics Inc.: Research Funding. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria. Hamadani:Pharmacyclics: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy. Ansell:LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Feldman:Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Takeda: Honoraria, Speakers Bureau. McGuirk:ArticulateScience LLC: Other: Assistance with manuscript preparation; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria. Manson:Bristol Myers Squibb: Honoraria. Orvain:Incyte: Honoraria; Novartis: Honoraria; Jazz Pharmaceuticals: Other: Travel & accommodations; Pfizer: Other: Travel & accommodations. Bouabdallah:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frigault:Novartis: Consultancy; Kite/Gilead: Honoraria; Nkarta: Consultancy; Incyte: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy. Chen:Takeda: Consultancy; Kiadis: Consultancy; Magenta: Consultancy; Abbvie: Consultancy; Incyte: Consultancy. Lynch:T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; Takeda Pharmaceuticals: Research Funding; Juno Therapeutics: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Smith:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Denovo Biopharma: Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Incyte Corporation: Research Funding; Ayala (spouse): Research Funding; Seattle Genetics: Research Funding. Byrne:Karyopharm: Research Funding. Cohen:Hutchison: Research Funding; Astra Zeneca: Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Genentech, Inc.: Consultancy, Research Funding; UNUM: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau. Armand:Sigma Tau: Research Funding; Otsuka: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Genentech: Research Funding. Zinzani: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; Sanofi: Consultancy; 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; MSD: Consultancy, Honoraria, 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; TG Therapeutics: Honoraria, Speakers Bureau. Carlo-Stella:Servier: Consultancy, Honoraria, Other: Travel, accommodations; Genenta Science srl: Consultancy; Boehringer Ingelheim: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations.

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Neuhaus, Paul. "United States Bureau of the Census989United States Bureau of the Census. United States Bureau of the Census, URL: http//www.census.gov." Electronic Resources Review 2, no. 2 (February 1998): 10–11. http://dx.doi.org/10.1108/err.1998.2.2.10.9.

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Caimi, Paolo, Brad S. Kahl, Mehdi Hamadani, Carmelo Carlo-Stella, Shui He, David Ungar, Jay Feingold, et al. "Safety and Efficacy of Adct-402 (Loncastuximab Tesirine), a Novel Antibody Drug Conjugate, in Relapsed/Refractory Follicular Lymphoma and Mantle Cell Lymphoma: Interim Results from the Phase 1 First-in-Human Study." Blood 132, Supplement 1 (November 29, 2018): 2874. http://dx.doi.org/10.1182/blood-2018-99-118133.

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Abstract Introduction: CD19, a B-cell surface antigen, is overexpressed in neoplastic lymphoid cells. ADCT-402 (loncastuximab tesirine; Lonca-T) is an antibody drug conjugate comprising a humanized monoclonal antibody directed against human CD19 conjugated through a pyrrolobenzodiazepine dimer toxin. This first-in-human clinical study evaluated the safety and efficacy of Lonca-T in patients (pts) with relapsed/refractory (R/R) B-cell lineage non-Hodgkin lymphoma. In the United States, follicular lymphoma (FL) is the most common indolent lymphoma and constitutes approximately 20% of all lymphomas, while mantle cell lymphoma (MCL) is rare and represents approximately 5% of all lymphomas. Here we present interim results in a subgroup of pts with FL and MCL; interim safety and efficacy of Lonca-T in pts with diffuse large B-cell lymphoma is presented in a separate abstract. Methods: Pts (≥18 years of age) with R/R FL and MCL who have failed or are intolerant to established therapies, or have no other treatment options available, were enrolled in this Phase 1, multicenter, open-label, and single-arm study including dose-escalation and dose-expansion parts. The primary objectives are to evaluate the safety and tolerability of Lonca-T, and determine the recommended dose(s) to use for expansion cohorts. The secondary objectives are to evaluate the clinical activity (measured by overall response rate [ORR], duration of response [DoR], progression-free survival [PFS] and overall survival), pharmacokinetics, pharmacodynamics, and anti-drug antibody activity. Pts received 1-hour intravenous infusions of Lonca-T every 3 weeks (Q3W; 1 cycle), with a 3+3 dose-escalation study design. No intra-pt dose-escalation is allowed. Results: As of June 20, 2018, 15 pts with FL (12 male, 3 female) and 15 with MCL (4 male, 11 female) had been enrolled in the study. The median ages of pts with FL and MCL were 58 years [range 40-75] and 64 years [range 51-87], respectively. Pts with FL had received a median 4 previous therapies (range 1-9), and those with MCL had received a median 4 prior therapies (range 1-13; Table), including prior ibrutinib therapy in 2/15 (13.3%) and 10/15 (66.7%) pts, respectively. Pts received doses of Lonca-T ranging from 15 to 200 µg/kg Q3W (FL, median cycles: 3 [range 2-11] and MCL, median cycles: 2 [range 1-11]). Of all pts with FL or MCL, treatment-emergent adverse events (TEAEs) were reported in 29/30 (96.7%) pts, and grade ≥3 TEAEs in 20 (66.7%) pts. The most common all-grade TEAEs (≥20% pts), regardless of relationship to study treatment, were fatigue (13 [43.3%]), increased gamma-glutamyltransferase (GGT) (13 [43.3%]), anemia (10 [33.3%]), myalgia (9 [30.0%]), increased alkaline phosphatase (8 [26.7%]), dyspnea (8 [26.7%]), nausea (8 [26.7%]), peripheral edema (8 [26.7%]), pleural effusion (8 [26.7%]), abdominal pain (7 [23.3%]), erythema (7 [23.3%]), decreased neutrophil count (7 [23.3%]), increased alanine transferase (6 [20.0]), increased aspartate aminotransferase (6 [20]), constipation (6 [20.0]), decreased appetite (6 [20.0]), and headache (6 [20.0]). The most common grade ≥3 TEAEs (>10% pts) were increased GGT (8 [26.7%]), decreased neutrophil count (6 [20.0%]), and anemia (4 [13.3%] pts). The figure depicts tumor response data for pts with FL and MCL. For the 15 evaluable pts with FL, the ORR was 80% (12/15 pts), comprising 8/15 (53.3%) complete responses (CRs) and 4/15 (26.7%) partial responses (PRs). The median DoR and PFS (responders and non-responders) were not reached in pts with FL after a median follow-up time of 7.56 months. Out of 15 evaluable pts with MCL, the ORR was 7/15 (46.7%), comprising 4/15 (26.7%) CRs and 3/15 (20.0%) PRs. In pts with MCL, median DoR was 5.3 months and PFS was 4.8 months after a median follow-up time of 5.78 months. Conclusions: In this Phase 1 study, Lonca-T has demonstrated encouraging single-agent antitumor activity and manageable toxicity in pts with R/R FL and MCL. Study sponsored by ADC Therapeutics. http://clinicaltrials.gov/show/NCT02669017. Figure. Figure. Disclosures Caimi: Genentech: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Kahl:Genentech: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Research Funding. Hamadani:Merck: Research Funding; ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Janssen: Consultancy; Takeda: Research Funding; Cellerant: Consultancy; Celgene Corporation: Consultancy; MedImmune: Consultancy, Research Funding; Ostuka: Research Funding. Carlo-Stella:Rhizen Pharmaceuticals: Research Funding; Sanofi: Consultancy; Boehringher Ingelheim Italia: Consultancy; MSD Italia: Speakers Bureau; Genenta Science: Speakers Bureau; AstraZeneca: Speakers Bureau; Amgen: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Janssen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau. He:ADC Therapeutics: Employment, Equity Ownership. Ungar:ADC Therapeutics: Employment, Equity Ownership. Feingold:ADC Therapeutics: Employment, Equity Ownership. Ardeshna:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Radford:ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Speakers Bureau; Celgene: Research Funding; BMS: Consultancy, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Equity Ownership; GlaxoSmithKline: Equity Ownership; Novartis: Consultancy, Speakers Bureau; Pfizer: Research Funding. Solh:Celgene: Speakers Bureau; ADC Therapeutics: Research Funding; Amgen: Speakers Bureau. Heffner:Kite Pharmaceuticals: Research Funding; ADC Therapeutics: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding. O'Connor:ADC Therapeutics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding.

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Pardanani, Animesh, Ayalew Tefferi, Tamas Masszi, Elena Mishchenko, Mark W. Drummond, Eric Jourdan, Alessandro M. Vannucchi, et al. "Fedratinib, an Oral, Selective Inhibitor of Janus Kinase 2 (JAK2), in Patients with Intermediate-2 or High-Risk Myelofibrosis (MF): Updated Results from the Randomized, Placebo-Controlled, Phase III JAKARTA Trial." Blood 136, Supplement 1 (November 5, 2020): 10–12. http://dx.doi.org/10.1182/blood-2020-137279.

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BACKGROUND: MF is characterized by anemia, splenomegaly, debilitating constitutional symptoms, and shortened survival. Fedratinib is an oral JAK2 inhibitor approved in the United States for treatment (Tx) of adult patients (pts) with intermediate (INT)-2 or high-risk MF. The randomized, placebo (PBO)-controlled, phase III JAKARTA trial evaluated clinical outcomes with fedratinib in pts with JAK-inhibitor-naïve MF. Initial findings from the JAKARTA study have been reported (Pardanani, JAMA Oncol, 2015). JAKARTA data were recently reanalyzed in preparation for regulatory review. OBJECTIVE: Evaluate the clinical efficacy and safety with fedratinib 400 mg/day in updated analyses of the JAKARTA study. METHODS: JAKARTA was an international, randomized, double-blind, PBO-controlled study that enrolled pts aged ≥ 18 years with INT-2 or high-risk primary, post-PV, or post-ET MF. Pts were randomly assigned 1:1:1 to fedratinib 400 mg, fedratinib 500 mg, or PBO, administered orally once-daily for ≥ 6 consecutive 4-week cycles ("randomized Tx period"). After completing 6 Tx cycles (or earlier in the case of disease progression), pts randomized to PBO could crossover to fedratinib. The primary endpoint was the spleen volume response rate (SVRR), the proportion of pts who achieved a ≥ 35% spleen volume reduction from baseline (BL) confirmed by MRI/CT at end of cycle 6 (EOC6), confirmed by follow-up scan 4 weeks later. Secondary endpoints included SVRR without 4-week confirmation, durability of spleen response, and symptom response rate (proportion of pts with a ≥ 50% reduction from BL in total symptom score [TSS] on the modified Myelofibrosis Symptom Assessment Form [MFSAF]) at EOC6. An exploratory analysis evaluated proportions of pts with ≥ 50% reductions from BL at EOC6 in individual MFSAF symptom scores: night sweats, pruritus, abdominal discomfort, early satiety, pain under ribs on left side, and bone or muscle pain. These analyses are limited to pts randomized to fedratinib 400 mg (the approved starting dose of fedratinib) or to PBO. Efficacy analyses were performed for the intention-to-treat (ITT) population and safety was assessed in all pts who received ≥ 1 dose of study drug. RESULTS: 96 pts were randomized to fedratinib 400 mg and 96 pts to PBO. In the fedratinib and PBO arms, median ages at BL were 63 (range 39-86) and 66 (27-85) years, respectively, 65% and 60% of pts had primary MF, 76% and 73% had constitutional symptoms, median spleen volumes were 2652 (316-6430) and 2660 (662-7911) mL, and median TSS were 15.3 (0-57) and 12.4 (0-53). Median durations of exposure were 15.5 months in the fedratinib 400 mg arm and 6 months in the PBO arm. With a confirmation scan 4 weeks after EOC6, SVRR was significantly higher in the fedratinib arm (37% [95%CI 27%, 46%]) vs. the PBO arm (1% [0%, 3%]) (P < 0.0001). Without the confirmation scan, SVRR at EOC6 was 47% (95%CI 37%, 57%) in the fedratinib 400 mg arm and 1% (0%, 3%) in the PBO arm (P < 0.0001; Figure). Estimated median duration of spleen response with fedratinib was 18.2 months. Symptom response rate at EOC6 for evaluable pts (ie, with TSS data available at BL and EOC6) was 40% (36/89) with fedratinib and 9% (7/81) with PBO (P < 0.0001). Fedratinib was associated with higher response rates vs. PBO in all 6 MFSAF symptoms: abdominal discomfort (41% vs. 15%, respectively), night sweats (58% vs. 22%), bone or muscle pain (33% vs. 14%), early satiety (51% vs. 18%), pruritus (39% vs. 20%), and pain under the ribs on the left side (42% vs. 24%). The most common Tx-emergent adverse events (TEAEs) during the randomized Tx period were grade 1-2 gastrointestinal events (Table). New or worsening grade 3 anemia and grade ≥ 3 thrombocytopenia laboratory abnormalities were reported in 34% and 12% of fedratinib-treated pts, most (75%) occurring within 3-4 months of Tx initiation. Compared with PBO, fedratinib-treated pts more frequently experienced increased serum creatinine, amylase, and lipase; these were mainly grade 1-2 in severity. TEAEs led to Tx discontinuation for 14% of fedratinib pts and 8% of PBO pts. CONCLUSIONS: Fedratinib 400 mg/day significantly reduced splenomegaly and symptom burden in pts with JAK-inhibitor-naïve MF. Relatively few pts discontinued fedratinib therapy due to TEAEs, suggesting these events are manageable. These data corroborate results initially reported for the JAKARTA trial, and further support the efficacy and safety of fedratinib in this pt population. Disclosures Masszi: AbbVie: 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; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Drummond:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: 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, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicine Corporation: Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jourdan:Novartis: Honoraria, 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; Abbvie: Membership on an entity's Board of Directors or advisory committees. Vannucchi:Blueprint: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: 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; Novartis: 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. Ribrag: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; BMS: 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; nanostring: Honoraria, Membership on an entity's Board of Directors or advisory committees; EPZ: Honoraria, Membership on an entity's Board of Directors or advisory committees; epizyme (EPZ): Research Funding; argenX: Research Funding; pharmamar: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; servier: Consultancy; gustave roussy comprehensive cancer center: Current Employment. Rambaldi:Abbvie: Honoraria; Jazz: Honoraria; Astellas: Honoraria; Omeros: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Roche: Honoraria; MSD: Honoraria. Rose:Bristol-Myers Squibb Company: Current Employment, Current equity holder in publicly-traded company. Zhang:Bristol-Myers Squibb Company: Current Employment, Current equity holder in publicly-traded company. Harrison:Promedior: Honoraria; Roche: Honoraria; Sierra Oncology: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Incyte Corporation: Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau; Janssen: Speakers Bureau; AOP Orphan Pharmaceuticals: Honoraria; CTI Biopharma Corp: Honoraria, Speakers Bureau.

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Crosswell, Howland E., Ann S. LaCasce, Nancy L. Bartlett, David J. Straus, Kerry J. Savage, Keenan Fenton, Gerald Engley, et al. "Brentuximab Vedotin with Chemotherapy in Adolescents and Young Adults (AYA) with Stage III or IV Hodgkin Lymphoma: A Subgroup Analysis from the Phase 3 Echelon-1 Study." Blood 132, Supplement 1 (November 29, 2018): 1647. http://dx.doi.org/10.1182/blood-2018-99-112907.

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Abstract Introduction: Hodgkin lymphoma (HL) is a rare disease that commonly occurs in AYAs, defined in the United States as patients 15 to 39 years of age. Brentuximab vedotin (Adcetris®; A) is an anti-CD30 antibody-drug conjugate approved for adult patients with previously untreated stage III or IV classical HL (cHL) in combination with doxorubicin, vinblastine and dacarbazine (AVD) chemotherapy based on results from the phase 3 ECHELON-1 trial which demonstrated a significantly improved modified progression-free survival (mPFS) compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (HR, 0.77; 95% CI, 0.60-0.98; P=0.04) (Connors JM, et al. N Engl J Med. 2018;378:331-344). Here we describe key efficacy and safety results for 18-to-39-year-old AYA patients enrolled in ECHELON-1. Methods: ECHELON-1 is a global, open-label, multicenter, randomized trial of patients with previously untreated stage III or IV cHL. Patients ≥18 years of age enrolled from both academic and community sites were randomized to receive A+AVD (n=664) or ABVD (n=670). The primary endpoint was mPFS, defined as progression, death, or receipt of additional anticancer therapy for patients who were not in complete response after completion of frontline therapy, as adjudicated by an independent review facility (IRF). Safety and tolerability was also assessed. To account for regional differences in the age ranges that define AYA patients, this exploratory subgroup analysis compares efficacy and key safety outcomes for AYA patients <30 and ≤39 years of age. Results: The AYA population consisted of 771 patients comprising 57.8% of the total trial population; the cohort comprised 303 patients aged 30 to 39 years, and 468 patients aged <30 years including 137 patients aged 18 to 21 years, 171 patients aged 22 to 25 years, and 160 patients aged 26 to 29 years. In patients aged <30 years, 244 received A+AVD and 224 received ABVD; in those ≤39 years of age, 396 received A+AVD and 375 received ABVD. Baseline demographics and disease characteristics were similar across age groups and treatments. The proportion of AYA patients treated in the Americas (40%), Europe (50%) and Asia (9%) reflected those of the overall trial population. Consistent with the overall trial population, median follow-up time was approximately 24 months for both age groups. AYA patients receiving A+AVD had an improved overall mPFS compared with patients receiving ABVD (≤39 years of age, HR 0.697 [95% CI, 0.495-0.980]; <30 years of age, HR 0.587 [95%CI, 0.376-0.916]) (Figure). The 2-year mPFS, also per IRF, for patients ≤39 years who received A+AVD was 84.6% vs 78.6% for those who received ABVD; patients aged <30 years receiving A+AVD also had improved 2-year mPFS compared with patients receiving ABVD (86.7% vs 74.4% respectively). Conventional PFS, as measured by investigators, was consistent with mPFS results for each age group: the HR for PFS in patients receiving A+AVD vs ABVD was 0.652 (95% CI, 0.449-0.945; P=0.023) in patients ≤39 years of age and 0.595 (95% CI, 0.367-0.965; P=0.033) in patients aged <30 years. The rate of treatment-emergent adverse events (TEAEs) in patients receiving A+AVD or ABVD was similar across age groups and reflected that of the overall trial population. TEAEs of interest include peripheral neuropathy (PN), febrile neutropenia (FN), and pulmonary-related toxicity (PRT). For patients receiving A+AVD or ABVD, any-grade PN occurred 64% and 40% of AYA patients; the majority (69%) of patients with PN had improvement/resolution of PN. The rate of FN in patients on A+AVD or ABVD arms was 16% and 5%, respectively; the incidence of FN was lower in patients who received G-CSF primary prophylaxis (9% and 5%, respectively). The incidence of PRT was low on both A+AVD (2%) and ABVD arms (4%). Conclusions : This exploratory analysis of ECHELON-1 demonstrated that AYAs receiving A+AVD had significantly improved mPFS with a manageable tolerability profile compared with AYA patients receiving ABVD. A+AVD can be considered a treatment option for AYAs with advanced-stage cHL. Additional data presented will focus on comparing results between AYA age ranges. Disclosures Crosswell: Seattle Genetics: Other: stock ownership in Seattle Genetics. LaCasce:Research to Practice: Speakers Bureau; Humanigen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Bristol-Myers Squibb: Other: Data safety and monitoring board. Bartlett:Affimed: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Bristol-Meyers Squibb: Research Funding; Merck & Co: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Novartis: Research Funding; Immune Design: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Gilead: 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; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding; Novartis: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; ImaginAB: Research Funding; Forty Seven: Research Funding. Straus:Medical Crossfire: Speakers Bureau; DAVA Oncology: Consultancy, Honoraria; InPractice Elselvier: Consultancy; JUNO: Consultancy; Bayer: Consultancy; Roch China: Speakers Bureau; Seattle Genetics: Consultancy; Memorial Sloan Kettering Cancer Center: Employment; Onco Tracker: Consultancy; Millenium (Takeda): Consultancy, Research Funding. Fenton:Seattle Genetics, Inc.: Employment, Equity Ownership. Engley:Seattle Genetics: Employment. Jolin:Takeda Pharmaceuticals International Co.: Employment. Liu:Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Zinzani:TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; TG Pharmaceuticals: 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, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: 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; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Collins:Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Amgen: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding; Celleron: Consultancy, Honoraria; MSD: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Celgene Corporation: Research Funding; Pfizer: Consultancy, Honoraria. Grigg:Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

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Guru Murthy, Guru Subramanian, Aniko Szabo, Mehdi Hamadani, Timothy S. Fenske, and Nirav N. Shah. "Improvements in Clinical Outcomes of Advanced Stage Classical Hodgkin Lymphoma in the United States from 2000-2014: Analysis of Surveillance Epidemiology and End Results Database." Blood 132, Supplement 1 (November 29, 2018): 2939. http://dx.doi.org/10.1182/blood-2018-99-116774.

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Abstract Background: Advanced Stage Hodgkin lymphoma (HL) is a curable malignancy with combination chemotherapy. While most patients are cured with frontline therapy, for those with refractory disease or early progression, historically, the outcomes have been poor. Novel therapies, PET/CT adapted treatment approaches, and improvement in transplantation have changed the management of both frontline and relapsed HL. However, it remains unknown if these developments have improved the clinical outcomes at population level over time. Methods: Using Surveillance Epidemiology and End Results database, we identified patients aged ≥ 18 years with advanced stage (Stage III or IV) pathologically confirmed classical HL as the first primary malignancy,diagnosed between the years 2000-2014, treated with chemotherapy and actively followed. Patients were stratified by date of diagnosis into 3 groups - 2000-2004, 2005-2009, 2010-2014 to assess the trends in overall survival (OS) over time. Race/ethnicity was stratified into non-hispanic whites and minorities (Non-hispanic blacks, Hispanics, other non-hispanic races). Kaplan-Meier method and log rank test were used to analyze the OS among subgroups. Cox proportional hazard regression method was used to determine the influence of period and demographic factors on OS.Cumulative incidence of death from cardiac cause was estimated using the Nelson-Aalen estimates. Statistical analyses were carried out with significant two sided p< 0.05. Results: A total of 9042 patients with a median age of 41 years were included. There were more males (60.1%) and non-Hispanic whites (64.2%) and most patients had nodal disease (98%) (Table 1).The use of frontline radiation therapy decreased in each 5-year time period (21.3% 2000-2004 vs 15.5% 2005-2009 vs 10.7% 2010-2014, p<0.001). In terms of survival, when stratified by the period of diagnosis, the 3-year OS was significantly higher for patients diagnosed between the year 2010-2014 (81.8%) and 2005-2009 (80.6%) than those diagnosed from 2000-2004 (78.5%, p=0.0008 and 0.02 respectively) (Figure 1). Additionally, age was a significant predictor for OS with a decreasing 3-year OS with increasing age (age < 40 - 91.1%, age 41-60 -81.5%, age >60 -54%, p< 0.001, Figure 2).While outcomes were poorest in the age>60 cohort, similar improvements were seen in OS over the three time periods among this patient population (48.6%- 2000-2004 vs 54.3% 2005-2009 vs 56.8% 2010-2014, p=0.005). On multivariate analysis, diagnosis in the earlier period was associated with higher mortality (2000-2004-HR 1.36, 95% CI 1.21-1.53, p< 0.001; 2005-2009 -HR 1.14, 95% CI 1.01-1.28, p=0.02, both compared to reference group 2010-2014). Similarly, minority races (HR 1.36, 95%CI 1.23-1.49, p<0.001) had a higher mortality risk as compared to non-Hispanic whites. Females (HR 0.82, 95%CI 0.75-0.90 p<0.001) and married status (HR 0.80, 95%CI 0.72-0.87, p< 0.001) were associated with significantly lower mortality. While radiation use decreased over time, the cumulative incidence of cardiac related cause of death did not vary significantly among the three-time periods (1.2% vs 1.1% vs 1.1% respectively at 48 months, p=0.85). Conclusions: Survival of patients with advanced stage HL has continued to improve over time suggesting the clinical impact of evolving treatment approaches. Interestingly this improvement has occurred despite the decreasing utilization of radiation therapy over time. This is suggestive of better end of treatment assessment with PET/CT eliminating the need for end of treatment radiation, improved second line therapies that extend survival, or potentially reduction in treatment related toxicities.Despite these encouraging results, the 3-year OS in the contemporary period remains inadequate at 81.8%. Furthermore, significant differences in survival continue to exist among non-modifiable factors such as gender, age, race, and marital status, highlighting the need for continued research to address these discrepancies. Results of this study provide a new baseline to test novel frontline combination regimens. Disclosures Hamadani: Takeda: Research Funding; Celgene Corporation: Consultancy; Cellerant: Consultancy; Ostuka: Research Funding; Janssen: Consultancy; MedImmune: Consultancy, Research Funding; Merck: Research Funding; ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau. Shah:Miltenyi: Other: Travel funding, Research Funding; Exelexis: Equity Ownership; Oncosec: Equity Ownership; Geron: Equity Ownership; Juno Pharmaceuticals: Honoraria; Lentigen Technology: Research Funding.

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WALDMAN, LILA. "Bilingual Administrative Support Personnel in United States Corporations." Modern Language Journal 78, no. 3 (September 1994): 327–38. http://dx.doi.org/10.1111/j.1540-4781.1994.tb02046.x.

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Pinto, Arthur R. "Takeovers of Public Corporations in the United States." American Journal of Comparative Law 34, suppl_1 (1986): 271–90. http://dx.doi.org/10.1093/ajcl/34.suppl1.271.

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Stoesz, David, and Howard Karger. "The Corporatisation of the United States Welfare State." Journal of Social Policy 20, no. 2 (April 1991): 157–71. http://dx.doi.org/10.1017/s0047279400018699.

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ABSTRACTThis article examines the increasing importance of human service corporations within the American welfare state. In particular, the article investigates the historical and philosophical background of the corporatisation of welfare, the expanding social welfare market, and the scope of human service corporations. The consequence of corporatisation, including standardisation, commodification, and the oligarchic nature of human services are also examined. Lastly, the authors explore the implications of corporatisation for the future of the US welfare state.

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Epperla, Narendranath, Jeffrey M. Switchenko, Krithika Shanmugasundaram, Subir Goyal, Oscar Calzada, Michael C. Churnetski, Bhaskar Kolla, et al. "Short Time to Treatment Is Associated with Inferior Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma." Blood 134, Supplement_1 (November 13, 2019): 3997. http://dx.doi.org/10.1182/blood-2019-128632.

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Introduction: Time to treatment (TTT) is an important prognostic factor in patients with newly diagnosed diffuse large B-cell lymphoma (Maurer et al JCO 2018) where patients who initiate therapy quickly after diagnosis have an inferior event free survival compared to those who do not require such immediate treatment initiation. More recently, TTT has shown to be associated with adverse clinical factors and inferior outcomes in mantle cell lymphoma (MCL; Maurer, et al ASH, 2018). However, there is a paucity of data on the impact of TTT on overall survival (OS). We sought to validate these findings and to evaluate the impact of TTT on survival outcomes in newly diagnosed patients with MCL. Methods: We included patients from 12 medical centers in the United States with MCL diagnosed between January 1, 2000, and January 1, 2018, who had information on the TTT and initiated treatment within 60 days of diagnosis (to exclude patients whose treatment was purposefully deferred). TTT was defined as the time in days from first lymphoma diagnosis to initiation of therapy. Patients who received treatment within 14 days were categorized into short TTT group. We compared differences between the two groups (TTT<=14 days vs TTT> 14 days and ≤ 60 days, longer TTT group) using chi-squared test, Fisher's exact tests, or ANOVA tests as appropriate. OS was defined as the time from diagnosis to death or last follow-up. Patients not experiencing an event were censored at their last known follow-up. OS was determined using the Kaplan-Meier method, and univariable and multivariable models were developed to identify predictors of OS. Results: Of 1,168 patients with newly diagnosed MCL, seven hundred fifty-five patients met the inclusion criteria and were included in this analysis, including 205 (27%) with short TTT and 550 (73%) with longer TTT. Median time to treatment was 7 days (range, 0-14) for the short TTT group vs 31 days for the longer TTT group (range, 15-60 days). The median age for the entire cohort was 63 years, 75% of patients were male, and 93% of patients had ECOG 0-1. The proportion of patients with stage 4 disease (93 vs 86%, p=0.015), elevated LDH (58 vs 39%, p<0.001), >3 cytogenetic abnormalities (29 vs 14%, p=0.005), B symptoms (47 vs 29%, p<0.001) and high MIPI score (49 vs 27%, p<0.001) was higher in short TTT group compared to longer TTT group. 65% received intensive induction therapy in the short TTT group relative to 57% in the longer TTT group (p=0.046) (Table). On univariable analysis, factors associated with inferior OS included, TTT<=14 days (HR=1.66, 95%CI=1.23-2.27, p<0.001), ECOG >=2 (p<0.001), stage IV disease (p=0.01), elevated LDH (p<0.001), WBC >10k (p=0.002), BM involvement (p<0.001), splenomegaly (p<0.001), ≥3 cytogenetic abnormalities (p<0.001), non-intensive regimen (p=0.03), B symptoms (p<0.001), and high MIPI score (p<0.001). With a median follow-up of 3.4 years, the median OS was 8.8 years (95%CI=7-NA) for patients with short TTT group and 12.5 years (95% CI: 11.4-18.7) for patients with longer TTT group (Figure; p<0.001). In the multivariable model including ECOG, LDH, intensive regimen and B symptoms, short TTT (HR=2, 95%CI=1.25-3.22; p=0.004), ECOG >=2 (HR=2.25, 95%CI=1.22-4.14; p=0.009), elevated LDH (HR=1.81, 95%CI=1.16-2.85; p=0.01), and receipt of non-intensive regimen (HR=1.61, 95%CI=1.04-2.50; p=0.03) were significant predictors of OS while B symptoms was not. Conclusions: Short TTT for patients with newly diagnosed MCL is associated with aggressive disease features and inferior OS despite an increased likelihood of receiving intensive induction regimens. Further studies are needed to identify molecular determinants of such aggressive disease behavior that can be assessed quickly and utilized to initiate appropriate therapy in a timely manner. Ongoing front-line clinical trials in MCL should be developed in a way to facilitate enrollment of patients requiring urgent therapy, including potentially permitting a cycle of off-study treatment to manage symptoms while a patient is screened and enrolled. Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Kolla:Amgen: Equity Ownership. Bachanova:GT Biopharma: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Gamida Cell: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Gerson:Seattle Genetics: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy. Barta:Mundipharma: Honoraria; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Danilov:Bristol-Meyers Squibb: Research Funding; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; AstraZeneca: Consultancy, Research Funding; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Genentech: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; MEI: Research Funding; Janssen: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Hill:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Ghosh:Forty Seven Inc: Research Funding; AbbVie: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Speakers Bureau; Genentech: Research Funding; Spectrum: Consultancy, Speakers Bureau. Park:Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; BMS: Consultancy, Research Funding. Hamadani:Pharmacyclics: Consultancy; Medimmune: Consultancy, Research Funding; Janssen: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene: Consultancy; Otsuka: Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding. Martin:I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Teneobio: Consultancy. Kahl:AbbVie Inc, Acerta Pharma - A member of the AstraZeneca Group, AstraZeneca Pharmaceuticals LP, BeiGene, Celgene Corporation, Genentech, Pharmacyclics LLC, an AbbVie Company, Roche Laboratories Inc.: Consultancy. Flowers:V Foundation: Research Funding; National Cancer Institute: Research Funding; Millenium/Takeda: Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Karyopharm: Consultancy; Spectrum: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Optimum Rx: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Bayer: Consultancy. Cohen:Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Janssen Pharmaceuticals: Consultancy.

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Staples, Clifford L. "The Politics of Employment-Based Insurance in the United States." International Journal of Health Services 19, no. 3 (July 1989): 415–31. http://dx.doi.org/10.2190/bf04-yydv-vm2r-lkdv.

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Analyses of the corporatization of U.S. health care typically focus on the political struggle between corporations and traditional health care providers, e.g., physicians. A neglected area of study is the struggle between corporations and their employees over the employment-based health insurance system. Yet, since this system is currently the primary mechanism for financing health care in the United States, an analysis of its historical development is critical to any understanding of the corporatization of U.S. health care. It is argued here that the employment-based health insurance system was a part of a political compromise between capital and labor that emerged after World War II. In exchange for control over production and increased worker productivity, corporations agreed to provide workers with steady wage increases and an expanded system of fringe benefits, or “corporate welfare.” But, by the late 1970s, rising health care costs created a corporate health care financing crisis that has prompted corporations to cut back employee health insurance coverage. The relative inability of workers to resist such cutbacks reveals the extent to which, by linking health care to wage labor, the “corporate welfare” system has made the U.S. working class more vulnerable to corporate power.

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Kumagai, Jean. "Several Japanese Corporations Establish New Labs in United States." Physics Today 44, no. 2 (February 1991): 81–83. http://dx.doi.org/10.1063/1.2809989.

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Dimopoulos, Meletios A., Katja Weisel, Philippe Moreau, Larry Anderson, Darrell J. White, Jesus F. San-Miguel, Pieter Sonneveld, et al. "Pomalidomide + Bortezomib + Low-Dose Dexamethasone Vs Bortezomib + Low-Dose Dexamethasone As Second-Line Treatment in Patients with Lenalidomide-Pretreated Multiple Myeloma: A Subgroup Analysis of the Phase 3 Optimismm Trial." Blood 132, Supplement 1 (November 29, 2018): 3278. http://dx.doi.org/10.1182/blood-2018-99-111869.

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Abstract BACKGROUND As lenalidomide (LEN) becomes increasingly established as a standard of care in the treatment (Tx) of newly diagnosed multiple myeloma (NDMM), patients (pts) for whom LEN is no longer a Tx option, including those who have become refractory to LEN, represent a clinical reality. These pts represent the largest population with MM at first relapse in the United States and a growing population globally. To date, they have been poorly studied and remain difficult to treat. Previous trials have demonstrated a clinical benefit with pomalidomide (POM) therapy in LEN-refractory pts with relapsed or refractory MM (RRMM), including those who were heavily pretreated (median of 5 prior regimens) (San Miguel et al. Lancet Oncol 2013; Richardson et al. Blood 2014; Dimopoulos et al. Blood 2016). These studies led to the approval of POM + low-dose dexamethasone (LoDEX) in RRMM. The pomalidomide, bortezomib, and low-dose dexamethasone (PVd) regimen has shown promising activity in early-phase clinical trials in LEN-refractory pts. In the phase 3 OPTIMISMM trial, PVd showed significantly improved progression-free survival (PFS) and a manageable safety profile compared with bortezomib and low-dose dexamethasone (Vd) in intent-to-treat population of pts who received 1-3 prior regimens and were 100% LEN pretreated; 70% of pts were LEN refractory (Richardson et al. ASCO 2018 abstract 8001). Here, we present efficacy and safety results in LEN-refractory and -nonrefractory pts treated at first relapse. METHODS Pts were randomized 1:1 to receive PVd or Vd in 21-day cycles: POM 4 mg/day on days 1-14 (PVd arm only); bortezomib (BORT) 1.3 mg/m2 on days 1, 4, 8, and 11 of cycles 1-8 and on days 1 and 8 of cycles 9+; and DEX 20 mg/day (10 mg/day if aged > 75 yrs) on the days of and after BORT. Key eligibility criteria included ≥ 2 cycles of prior LEN therapy, including LEN-refractory pts. BORT-exposed pts were eligible to enroll, provided they did not have progressive disease during therapy or within 60 days of the last dose of a BORT-containing regimen with BORT dosed at 1.3 mg/m2 twice weekly. The primary endpoint was PFS. RESULTS Out of 559 pts enrolled patients, 226 were treated in the second line (2L), data cut off October 26, 2017: 111 with PVd and 115 with Vd. Median follow-up for 2L pts was 16.4 mos. Among 2L pts, 129 (57.1%) were LEN refractory (64 PVd; 65 Vd) and 97 (42.9%) were LEN nonrefractory (47 PVd; 50 Vd). In LEN-refractory pts (PVd vs Vd) median age was 68.0 vs 69.0 yrs, 57.8% vs 58.5% were male, and 56.3% vs 47.7% had prior BORT. In LEN-nonrefractory pts, median age was 66.0 vs 65.5 yrs, 63.8% vs 38% were male, and 66.0% vs 72.0% had prior BORT. Other key baseline characteristics were similar between Tx arms and subgroups. Median PFS was 17.8 mos with PVd vs 9.5 mos with Vd in LEN-refractory (HR 0.55; 95% CI, 0.33-0.94; Figure 1A) and 22.0 vs 12.0 mos in LEN-nonrefractory pts (HR 0.54; 95% CI, 0.29-1.01; Figure 1B). Response outcomes are shown in Figure 2. ORR was 85.9% with PVd vs 50.8% with Vd in LEN-refractory pts (P < .001) and 95.7% vs 60.0% in LEN-nonrefractory pts (P < .001). In 2L LEN-refractory pts, the most common grade 3 or 4 treatment-emergent adverse events (TEAEs) with PVd vs Vd were neutropenia (35.9% vs 12.9%), thrombocytopenia (17.2% vs 22.6%), and anemia (17.2% vs 8.1%). Grade 3 or 4 infections occurred in 29.7% vs 21.0% of pts. In 2L LEN-nonrefractory pts, the most common grade 3 or 4 TEAEs were neutropenia (36.2% vs 6.3%) and thrombocytopenia (23.4% vs 18.8%). Grade 3 or 4 infections occurred in 27.7% vs 8.3% of pts. In 2L LEN-refractory pts, median Tx duration of PVd vs Vd was 9.7 vs 6.1 mos. In 2L LEN-nonrefractory pts, median Tx duration of Pvd vs Vd was 13.6 vs 6.6 mos. CONCLUSIONS To date, OPTIMISMM is the only phase 3 trial to address Tx of pts with RRMM following LEN exposure in early lines and the first to report data in LEN-refractory pts after first relapse. PVd reduced the risk of progression and death by 45% and 46% vs Vd in LEN-refractory and -nonrefractory pts, respectively. Further, in both subgroups, 2L Tx with PVd significantly improved ORR and led to deeper responses compared with Vd. AEs with PVd therapy were generally consistent with the known AEs of POM, BORT, and DEX. These data further demonstrate that PVd is effective and tolerable in pts for whom LEN is no longer a Tx option, including LEN-refractory pts, supporting its use as 2L therapy in RRMM. Disclosures Dimopoulos: Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria. Weisel:Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moreau:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Anderson:Celgene: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau. White:Amgen: 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; Janssen: 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. San-Miguel:Celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Roche: Honoraria; BMS: Honoraria; Novartis: Honoraria. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Jenner:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau. Dürig:Janssen: Consultancy, Honoraria; Celgene: Honoraria; Roche: Honoraria, Speakers Bureau. Pavic:AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Salomo:Cilag: Consultancy; Janssen: Consultancy. Yu:Celgene: Employment, Equity Ownership. Nguyen:Celgene Corporation: Employment. Bensmaine:Celgene: Equity Ownership. Peluso:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Richardson:BMS: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: 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; Amgen: Membership on an entity's Board of Directors or advisory committees.

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Barosi, Giovanni, Mohan Agarwal, Sonja Zweegman, Wolfgang Willenbacher, Sima Pakstyte, Reinier Raymakers, Nathan Cantoni, et al. "An Individual Patient Supply Program for Ruxolitinib for the Treatment of Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF)." Blood 120, no. 21 (November 16, 2012): 2844. http://dx.doi.org/10.1182/blood.v120.21.2844.2844.

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Abstract Abstract 2844 Background: Myeloproliferative neoplasms, including PMF, PET-MF, and PPV-MF, are a group of clonal stem cell–derived diseases characterized by bone marrow fibrosis, splenomegaly, and debilitating constitutional symptoms. Ruxolitinib (rux), a potent oral JAK1 & 2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life in 2 phase 3 studies (COMFORT-I and -II). Due to unmet medical need, rux has been made available through an individual patient supply program (IPSP) outside the US. Methods: Patients (pts) with PMF, PPV-MF, or PET-MF requiring treatment (as determined by their physician) and classified as high-, intermediate (int)-2–, or int-1–risk with an enlarged spleen were evaluated for eligibility on an individual basis by the sponsor, irrespective of JAK2 mutation status. The starting dose of rux was determined on the basis of baseline platelet count (15 or 20 mg twice daily for pts with platelet counts of 100–200 × 109/L and > 200 × 109/L, respectively) and can be adjusted for efficacy and safety. Dose changes during treatment, adverse events (AEs), and serious AEs (SAEs) are registered throughout the program. Results: To date, 1339 requests have been received from > 800 physicians in 48 countries, including locations in Europe, Latin America, the Middle East, and Asia. The baseline characteristics are shown in the Table for pts whose requests for access were approved (n = 1240). Drug resupply requests are received every ≈ 3 months. Follow-up information, based on the first resupply request, was available for 381/639 (60%) of the pts who were enrolled in the program prior to February 2012; 303 (80%) remain on rux therapy, 37 (10%) have discontinued, 11 (3%) died, and 30 (8%) did not initiate therapy. Spleen response was available for 247 pts (decreased, n = 201; unchanged, n = 39; increased, n = 7). Changes in constitutional symptoms were available for 203 pts (decreased, n = 151; unchanged, n = 49; increased, n = 3). In pts enrolled in the IPSP undergoing rux treatment, most pts who had a decrease in spleen length also had a decrease in symptoms. Dose-modification information was available for 259 pts, of whom 44 had dose increases and 89 had dose decreases. Reasons for dose modifications included efficacy (n = 28), safety (n = 69), and other reasons (n = 36). Safety information was available for 266 pts; 75 reported significant AEs or SAEs as determined by investigators. Enrolled pt characteristics are generally similar to those expected in the overall MF pt population. Thus far, the proportion of pts enrolled in the IPSP with the JAK2 V617F mutation (73%) is higher than that for the general MF population (50%-60%). This may reflect a misconception that JAK inhibition is primarily effective in pts who have the JAK2 V617F mutation, when in fact rux has demonstrated similar efficacy in both pt types in the phase 1/2 251 study and the two phase 3 COMFORT trials. This may also be reflected in the higher proportion of PPV-MF pts in the IPSP than in the general MF population (28% vs 10%-15%), of whom 95% are JAK2 V617 F–positive. Conclusions: Considerable requests for access to rux have been received through the IPSP, highlighting the need for an effective treatment in pts with a range of IPSS risk-assessment scores. The demographics of the IPSP pts are similar to those expected in the overall MF population. Responses and safety patterns observed in the IPSP appear to be comparable to those from the COMFORT trials. Disclosures: Off Label Use: Jakafi™ (ruxolitinib) is indicated in the United States for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis and post–essential thrombocythemia myelofibrosis. In Canada, JAKAVI ® is indicated for the treatment of splenomegaly and/or its associated symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. This abstract reports on a clinical study conducted outside the US including patients of all risk categories. All patients have provided written informed consent. Zweegman:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Willenbacher:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Raymakers:Novartis: Consultancy. Cantoni:CSL Behring Switzerland: Research Funding; Robapharm/Pierre Fabre Oncology Switzerland: Research Funding; Janssen-Cilag Switzerland: Consultancy; Novartis Oncology Switzerland: Consultancy, Research Funding. Modi:Novartis Pharmaceuticals Corporation: Employment. Khan:Novartis: Employment. Perez:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Gisslinger:AOP Orphan Pharmaceuticals AG: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Lavie:Novartis: Membership on an entity's Board of Directors or advisory committees. Harrison:Sanofi Aventis: Honoraria; YM Bioscience: Consultancy, Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Research Funding.

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George, Tracy I., Harry P. Erba, David P. Steensma, Daniel A. Pollyea, Mehrdad Abedi, Rafael Bejar, Christopher R. Cogle, et al. "Current Diagnosis Patterns for Acute Myeloid Leukemia (AML) in Clinical Practice Compared with World Health Organization (WHO) 2008 Recommendations: Outcomes from the CONNECT® Myelodysplastic Syndromes (MDS) and AML Disease Registry." Blood 128, no. 22 (December 2, 2016): 3548. http://dx.doi.org/10.1182/blood.v128.22.3548.3548.

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Abstract Background: The diagnosis of AML requires an integrated approach of clinical, morphologic, cytogenetic, and molecular assessments. The CONNECT MDS/AML Disease Registry (NCT01688011) is a prospective, longitudinal, multicenter, observational cohort study of patients (pts) in the United States with newly diagnosed AML, MDS, or idiopathic cytopenia of undetermined significance, designed to evaluate diagnostic and treatment (Tx) patterns, clinical and pt-reported outcomes, and correlative data, such as genetic mutations. This investigation was performed to assess how pts with AML are diagnosed at community and academic sites and compare how these diagnostic practices align with WHO 2008 recommendations for AML. Methods: Pt enrollment began in December, 2013 and will continue until ~1500 pts from ~150 US sites are enrolled. Target enrollment for the AML cohort is 400 pts. To best capture the typical distribution of clinical practice settings in which AML pts are treated, ~80% of the sites will be community-based and ~20% will be academic institutions (ie, affiliated with a medical school). Pts aged ≥55 years (yrs) with newly diagnosed AML (excluding acute promyelocytic leukemia) are eligible. All decisions regarding pt care (Tx, testing) are determined by the study clinician, as the disease registry is non-interventional. AML diagnosis is confirmed by independent central review of all available diagnostic test reports, including bone marrow (BM) aspirates and biopsies, cytogenetics, molecular testing, and laboratory results. Diagnostic procedures are recorded in an electronic data capture system. Pt data will be entered quarterly for up to 8 years of follow-up. Results: Between December 12, 2013 and May 19, 2016, 180 AML pts have enrolled in the registry from 73 sites; 125 pts (69%) enrolled at a community site (including 1 governmental site) and 55 pts (31%) enrolled at an academic center. Median age of all pts was 71 yrs (range 55-91), with 72% of pts aged ≥65 yrs (Table 1). Blast percentages were reported in 97% of cases, mainly in BM, although peripheral blood blasts were also assessed for 71% of pts (Table 2). Manual differential blast count was reported for 63% of pts, and flow cytometry and immunohistochemistry were used to determine blast counts for 10% of pts each. Immunophenotyping by flow cytometry was reported for 97% of pts. Erythroid, megakaryocytic, or neutrophilic dysplasia, and presence or absence of Auer rods, ring sideroblasts, or fibrosis were reported for <50% of all pts (Table 2). Conventional karyotyping was performed for 90% of pts and FISH testing was reported for 80% of pts (Table 3). Mutation testing was reported for 85 pts (47%). Conclusions: The ongoing prospective CONNECT MDS/AML registry is uniquely positioned to assess current clinical practice patterns in AML. Flow cytometry and conventional karyotyping were done in most cases; however, manual blast count was missing for 37% of AML pt samples at diagnosis. Instead, ~10% of blasts counts were evaluated by flow cytometry or immunohistochemistry, and ~18% by 'other' means (ie, blast count estimations). Flow cytometry for blast enumeration is discouraged in WHO 2008 recommendations, as it may both under- and overestimate counts. Despite a 90% rate of conventional karyotyping, FISH testing was reported for 80% of pts, suggesting FISH may be used more than is necessary. Mutation testing was reported for approximately one-half of pts, which may reflect a lack of testing, a lag in mutational test reporting, or a combination of both. Diagnostic practices for AML pts enrolled thus far appear to be guided by WHO 2008 recommendations; awareness of updated recommendations may change diagnostic patterns as new AML pts enter the CONNECT MDS/AML registry. Disclosures George: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Allakos: Research Funding; Allakos: Research Funding; Blueprint Medicines: Consultancy; Novartis: Consultancy; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy; GLG: Consultancy; Wiley Blackwell: Consultancy; American Registry of Pathology: Patents & Royalties; Wolters Kluwer: Patents & Royalties; UpToDate: Patents & Royalties. Erba:Sunesis: Consultancy; Novartis: Consultancy, Speakers Bureau; Celator: Research Funding; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Juno: Research Funding; Astellas: Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Agios: Research Funding; Pfizer: Consultancy; Gylcomimetics: Other: DSMB; Millennium Pharmaceuticals, Inc.: Research Funding; Celgene: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Daiichi Sankyo: Consultancy. Steensma:Amgen: Consultancy; Ariad: Equity Ownership; Millenium/Takeda: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Genoptix: Consultancy. Pollyea:Alexion: Other: advisory board; Ariad: Other: advisory board; Celgene: Other: advisory board, Research Funding; Glycomimetics: Other: DSMB member; Pfizer: Other: advisory board, Research Funding. Abedi:Celgene: Consultancy. Bejar:Genoptix: Consultancy. Grinblatt:Celgene Corporation: Consultancy, Speakers Bureau. Komrokji:Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Revicki:Celgene: Consultancy. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy. Savona:TG Therapeutics: Research Funding; Takeda: Research Funding; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; Ariad: Membership on an entity's Board of Directors or advisory committees. Scott:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Thompson:VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Multiple Myeloma International Registry; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: MDS/AML Registry; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; AIM Specialty Health: 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. Fliss:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Nifenecker:Celgene: Employment, Equity Ownership. Kiselev:Celgene: Employment, Equity Ownership. Sugrue:Celgene Corporation: Employment, Equity Ownership. Foucar:Celgene: Membership on an entity's Board of Directors or advisory committees; ASCP press: Other: Book royalties; Elsevier: Other: Book royalties; Lippincott WW: Other: Book royalties.

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Nooka, Ajay K., Andrew J. Yee, Carol Ann Huff, Dan T. Vogl, Maria Gavriatopoulou, Ajai Chari, Philippe Moreau, et al. "Influence of Cytogenetics in Patients with Relapsed Refractory Multiple Myeloma Treated with Oral Selinexor and Dexamethasone: A Post-Hoc Analysis of the STORM Study." Blood 134, Supplement_1 (November 13, 2019): 1872. http://dx.doi.org/10.1182/blood-2019-122908.

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Introduction: Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) which forces nuclear retention and activation of tumor suppressor proteins. Selinexor plus low dose dexamethasone (Sel-dex) was recently approved in the United States based on data from the STORM study wherein, Sel-dex induced an overall response rate (ORR) of 26.2% in patients with penta-exposed, triple-class refractory multiple myeloma. The presence of high-risk cytogenetic abnormalities is known to have a poor prognosis in multiple myeloma, with transient responses. We performed post-hoc analyses to determine the outcomes in patients with relapsed/refractory myeloma treated with Sel-dex based on the baseline cytogenetic abnormalities. Methods: STORM was a phase 2b, open-label study which enrolled patients with relapsed and refractory myeloma. Selinexor 80 mg in combination with dexamethasone 20 mg was administered orally, twice weekly. The primary endpoint was ORR. For this analysis, we pooled 78 patients (48 quad-refractory and 30 penta-refractory) from STORM, part 1 and 122 patients (penta-exposed and triple class refractory) from STORM, part 2 to compare outcomes between high-risk and standard risk cytogenetics groups. High-risk cytogenetics was defined as having at least 1 of the following abnormalities by fluorescence in-situ hybridization (FISH) at baseline: del(17p), t(4;14), t(14;16), and gain(1q) in >5% of screened plasma cells. The FISH analyses were performed at a central laboratory and used to assess cytogenetic risk status. Results: Of the 200 patients, 122 (61%) had high-risk disease (del(17p): 36%, t(4;14): 18%, t(14;16): 5%, and gain(1q): 36%). The ORR in high-risk patients was 20.5% (very good partial response [VGPR)]: 5.7% and partial response [PR]: 14.8%) and the ORR was 29.5 % (complete response [CR]: 2.6%, VGPR: 3.8%, and PR: 23.1%) in standard-risk patients. The clinical benefit rate (CBR) was 35.2% in high-risk patients compared with 38.5% in standard-risk patients. Median duration of clinical benefit (DOCB) was 4.4 and 6.2 months in the high-risk and standard-risk patients respectively. Median progression-free survival (PFS) was 3.8 and 4.2 months and overall survival (OS) was 8.6 and 9.4 months in the high-risk and standard-risk patients, respectively. Efficacy by specific cytogenetic abnormality is presented in Table 1 below (Due to the small sample size (n=11), data for the t(14;16) subgroup are not presented separately). Conclusions: Sel-dex demonstrated a similar CBR in patients with high risk and standard risk disease and preserved clinical benefit in heavily pre-treated patients who had rapidly proliferative disease and high-risk cytogenetics at baseline. The benefit was maintained across cytogenetic risk subgroups with a higher ORR in the t(4;14) and gain(1q) subgroups. The DOR and OS was similar across all the subgroups. These analyses support the use of Sel-dex in patients with high-risk cytogenetics and warrant further evaluation of selinexor in combination with other anti-myeloma therapies in high-risk disease. Disclosures Nooka: GSK: Honoraria, Other: advisory board participation; Amgen: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation; Janssen: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; Celgene: Honoraria, Other: advisory board participation; Takeda: Honoraria, Other: advisory board participation. Yee:Adaptive: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Huff:Karyopharm, Sanofi, MiDiagnostics: Consultancy; Member of Safety Monitoring Board for Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Vogl:Karyopharm Therapeutics: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Active Biotech: Consultancy. Chari:Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: 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, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Oncoceutics: Research Funding. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; alexion: Consultancy; Janssen: Consultancy. Lonial:Genentech: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; BMS: Consultancy; Janssen: Consultancy, Research Funding; GSK: Consultancy; Celgene Corporation: Consultancy, Research Funding. Dimopoulos:Sanofi Oncology: Research Funding. Vij:Takeda: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Genentech: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Tuchman:Karyopharm: Honoraria; Celgene: Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding; Merck: Research Funding; Prothena: Research Funding; Roche: Research Funding; Sanofi: Research Funding; Alnylam: Honoraria, Research Funding. Biran:Bristol Meyers Squibb: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Siegel:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Richardson:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: 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. Liu:Karyopharm Therapeutics: Employment, Equity Ownership. Joshi:Karyopharm Therapeutics: Employment, Equity Ownership. Shah:Karyopharm Therapeutics: Employment, Equity Ownership. Shacham:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kauffman:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Jagannath:Medicom: Speakers Bureau; Multiple Myeloma Research Foundation: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Merck: Consultancy.

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Chernova, O. V., and D. H. Zaiats. "The Role of TNCs in U.S. Economic Strategy." Business Inform 5, no. 520 (2021): 42–48. http://dx.doi.org/10.32983/2222-4459-2021-5-42-48.

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The article is aimed at analyzing the impact of American transnational corporations (TNCs) on the economic strategy of the United States of America. During the research, the essence of the category of «transnational corporation» is considered and the peculiarities of functioning of the leading TNCs are defined. The key vectors of U. S. economic strategy at the present stage are specified. The activities of transnational (multinational) corporations in the United States of America is analyzed. The article carries out a comprehensive analysis of the existing ratings of American transnational corporations. The key indicators of their activity in various spheres of public production and sectors of economy are analyzed. The impact of transnational corporations on the U.S. economy is evaluated by analyzing the dynamics of exports, imports, indices of gross domestic product (GDP) and gross domestic product per capita. The activities of American TNCs in the territories of foreign countries is studied. The analysis of the dynamics of direct foreign investment of the United States of America abroad and the scale of investment in the national economy of the country from abroad is carried out. The geographical structure of foreign direct investment from the United States of America is considered. Existing threats to the U.S. economy caused by transnational corporations are identified, and their consequences are estimated. Conclusions have been drawn on the future prospects of transnationalization of the US economy and the impact of global companies on the economic strategy of the United States of America.

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Palumbo, Antonio, Meletios A. Dimopoulos, Philippe Moreau, Wee-Joo Chng, Hartmut Goldschmidt, Roman Hájek, Thierry Facon, et al. "Carfilzomib and Dexamethasone Vs Bortezomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: Results of the Phase 3 Study Endeavor (NCT01568866) According to Age Subgroup." Blood 126, no. 23 (December 3, 2015): 1844. http://dx.doi.org/10.1182/blood.v126.23.1844.1844.

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Abstract Introduction: Carfilzomib is a selective proteasome inhibitor that is approved in the United States and other countries for the treatment of relapsed and refractory multiple myeloma. The randomized, open-label, multicenter, phase 3 study ENDEAVOR (NCT01568866) met its primary end point, demonstrating a statistically and clinically significant improvement in progression-free survival (PFS) for carfilzomib and dexamethasone (Kd) compared with bortezomib and dexamethasone (Vd) (median 18.7 vs 9.4 months; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.44-0.65; 1-sided P <0.001) (Dimopoulos et al, J Clin Oncol 2015;33:abstr 8509; Dimopoulos et al, Haematologica 2015;100[s1]:abstr LB2071). Herein we present results of a preplanned subgroup analysis of efficacy and safety outcomes of the ENDEAVOR study according to age. Methods: Adult patients with relapsed multiple myeloma (RMM; 1-3 prior regimens) were eligible. Patients in the Kd arm received K (30-min intravenous [IV] infusion) on days (D) 1, 2, 8, 9, 15, and 16 (20 mg/m2 on D1, 2 [cycle 1]; 56 mg/m2 thereafter) and dexamethasone (20 mg) on D1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles. The Vd arm received V (1.3 mg/m2; IV or subcutaneously) on D1, 4, 8, and 11 and dexamethasone (20 mg) on D1, 2, 4, 5, 8, 9, 11, and 12 of 21-day cycles. Treatment was administered until disease progression or unacceptable toxicity. The primary end point of the study was PFS; secondary end points included overall survival, overall response rate (ORR), duration of response (DOR), safety, and rate of peripheral neuropathy (PN). The present analyses evaluated outcomes in patients grouped according to age (ie, <65, 65-74, and ≥75 years of age). Results: A total of 929 patients were enrolled (intent-to-treat population; <65 years: Kd, n=223; Vd, n=210; 65-74 years: Kd, n=164; Vd, n=189; ≥75 years: Kd, n=77; Vd, n=66). Baseline patient and disease characteristics were generally well balanced between treatment arms within each age subgroup. PFS was improved with Kd vs Vd within each age subgroup (<65 years: median, not estimable vs 9.5 months [HR, 0.58; 95% CI, 0.44-0.77]; 65-74 years: median, 15.6 months vs 9.5 months [HR, 0.53; 95% CI, 0.38-0.73]; ≥75 years: median, 18.7 months vs 8.9 months [HR, 0.38; 95% CI, 0.23-0.65]) (Table). Kaplan-Meier PFS curves by age subgroup are shown in the Figure. ORRs in each age group were also higher in the Kd arm compared with the Vd arm in each subgroup (<65 years: 74% vs 61% [odds ratio, 1.82; 95% CI, 1.21-2.74]; 65-74 years: 77% vs 66% [odds ratio, 1.80; 95% CI, 1.12-2.89]; ≥75 years: 84% vs 59% [odds ratio, 3.75; 95% CI, 1.71-8.24]). Rates of grade ≥3 adverse events of interest, including hypertension are shown in the Table. Grade ≥3 hypertension, dyspnea, cardiac failure, renal failure were more common with Kd vs Vd within each age subgroup. Rates of grade ≥2 PN were lower in the Kd arm across all subgroups compared with the Vd arm (<65 years: 6% vs 27% [odds ratio, 0.17; 95% CI, 0.09-0.32]; 65-74 years: 8% vs 34% [odds ratio, 0.17; 95% CI, 0.09-0.32]; ≥75 years: 3% vs 43% [odds ratio, 0.035; 95% CI, 0.008-0.16]). Adverse events leading to treatment discontinuation occurred at similar frequencies in the Kd and Vd arms in the two younger-age subgroups (<65 years: 17% vs 15%; 65-74 years: 22% vs 22%), but at a higher frequency in the Vd arm for the oldest-age subgroup (≥75 years: 26% vs 35%). Deaths within 30 days post-treatment due to adverse events occurred at similar rates in the Kd and Vd arms within each age subgroup (<65 years: 3% vs 3%; 65-74 years: 5% vs 3%; ≥75 years: 4% vs 5%). Conclusions: Kd demonstrated clinically meaningful improvement in PFS and ORR compared with Vd within all age subgroups examined, with a trend toward a greater improvement in the eldest-age subgroup (≥75 years) than in the two younger-age subgroups (<65 and 65-74 years). The eldest-age subgroup in the Kd arm had an increased incidence of select grade ≥3 adverse events of interest, including cardiac failure and hypertension, compared with the younger-age subgroups in the Kd arm. Hypertension is a recognized but manageable complication in elderly patients and should be monitored. Overall, results suggest that Kd has a favorable benefit-risk profile in patients with RMM, irrespective of age. Disclosures Palumbo: Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria. Dimopoulos:Janssen: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Genesis: Honoraria; Janssen-Cilag: Honoraria. Moreau:Novartis, Janssen, Celgene, Millennium, Onyx Pharmaceuticals: Consultancy, Honoraria. Goldschmidt:Janssen, Celgene, Novartis: Consultancy, Honoraria, Research Funding; Onyx: Consultancy, Honoraria; Amgen, Takeda: Consultancy; BMS: Consultancy, Research Funding; Chugai, Millennium: Honoraria, Research Funding. Hájek:Janssen-Cilag: Honoraria; Celgene, Amgen: Consultancy, Honoraria. Facon:Onyx/Amgen: Membership on an entity's Board of Directors or advisory committees. Ludwig:Janssen Cilag: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Onyx: Honoraria, Speakers Bureau; Celgene Corporation: Honoraria, Speakers Bureau; Takeda: Research Funding. Niesvizky:Celgene, Millennium, Onyx: Consultancy, Speakers Bureau. Oriol:Celgene, Janssen, Amgen: Consultancy, Speakers Bureau. Rosiñol:Celgene, Janssen: Honoraria. Gaidano:Celgene: Research Funding; Morphosys, Roche, Novartis, GlaxoSmith Kline, Amgen, Janssen, Karyopharm: Honoraria, Other: Advisory Boards. Weisel:Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel Support; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel Support; Janssen: Consultancy, Honoraria, Other: Travel Support, Research Funding; Onyx: Consultancy, Honoraria; Novartis: Other: Travel Support; Takeda: Other: Travel Support; Noxxon: Consultancy. Gillenwater:Onyx, Amgen: Employment, Other: Stock. Mohamed:Onyx/Amgen: Employment, Other: Stock. Feng:Amgen/Onyx: Employment, Equity Ownership. Joshua:Celgene: Membership on an entity's Board of Directors or advisory committees.

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Broome, Frederick R., Carl S. Hantman, Robert W. Marx, and Timothy F. Trainor. "Automated Mapping at the United States Census Bureau: 1980-1994." Cartography and Geographic Information Systems 22, no. 2 (January 1995): 128–34. http://dx.doi.org/10.1559/152304095782540429.

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Clark, G. L. "Problematic Status of Corporate Regulation in the United States: Towards a New Moral Order." Environment and Planning A: Economy and Space 24, no. 5 (May 1992): 705–25. http://dx.doi.org/10.1068/a240705.

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Evidence on the geographical dimensions of corporate restructuring in the United States suggests that, if left to themselves, corporations often break the law or at least the spirit of law in furthering their economic interests. The design and implementation of restructuring involving the spatial relocation of work is in many instances conceived with the goal of circumventing corporations' social obligations. Workers' pension entitlements (and their contractual agreements with corporations on many other matters) are at risk when the economic imperatives of competition and technical innovation are the driving forces behind corporations' actions. These issues are explored with respect to rational choice theory, advancing an argument to the effect that if corporate restructuring is only understood in these terms, the prospects for effective public regulation are bleak indeed. A regulatory framework that explicitly references moral standards could be, however, more effective because the terms of evaluation would be legitimately other than simple benefit-cost analysis. This last argument is briefly illustrated by reference to the moral component inherent in making contracts between agents.

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Pinto, Arthur. "An Overview of United States Corporate Governance in Publicly Traded Corporations." American Journal of Comparative Law 58, no. 1 (January 1, 2010): 257–83. http://dx.doi.org/10.5131/ajcl.2009.0036.

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Choi, Young-Ran. "General Jurisdiction over Foreign Corporations in the United States Civil Procedure." Wonkwang University Legal Research Institute 34, no. 4 (December 30, 2018): 225–41. http://dx.doi.org/10.22397/wlri.2018.34.4.225.

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Bratt, Rachel G., and William M. Rohe. "Challenges and dilemmas facing community development corporations in the United States." Community Development Journal 42, no. 1 (August 17, 2005): 63–78. http://dx.doi.org/10.1093/cdj/bsi092.

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Hashmi, M. Anaam, Amal Damanhouri, and Divya Rana. "Evaluation of Sustainability Practices in the United States and Large Corporations." Journal of Business Ethics 127, no. 3 (February 5, 2014): 673–81. http://dx.doi.org/10.1007/s10551-014-2056-4.

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Gray, Dahli. "IFRS And US GAAP Convergence Progressing: As Taxpayers Voluntarily Stop Using LIFO." International Business & Economics Research Journal (IBER) 12, no. 4 (March 27, 2013): 451. http://dx.doi.org/10.19030/iber.v12i4.7743.

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This paper presents the potential benefits of the last in, first out (LIFO) inventory valuation method being eliminated as a requirement in financial statements prepared under United States Generally Accepted Accounting Principles when also used for United Stated federal income tax reporting. Research results show that corporations have been voluntarily switching from LIFO to another method since inflation declined well below double digits. Of the corporations still using LIFO, the potential billions of federal tax revenue is presented that might help keep the United States federal budget from going over the fiscal cliff.

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Golden, J., and J. P. Brosco. "The United States Children's Bureau and Pediatric Medicine: A Retrospective Analysis." PEDIATRICS 130, no. 6 (November 19, 2012): 993–95. http://dx.doi.org/10.1542/peds.2012-1865.

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Hummer, Don. "United States Bureau of Prisons’ Response to the COVID-19 Pandemic." Victims & Offenders 15, no. 7-8 (October 2, 2020): 1262–76. http://dx.doi.org/10.1080/15564886.2020.1829765.

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Schwarzkopf, Leroy C. "United States Census Bureau CD-ROM evaluation project: A news note." Government Publications Review 14, no. 3 (January 1987): 353–54. http://dx.doi.org/10.1016/0277-9390(87)90071-9.

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Tsui, Anne S., Georges Enderle, and Kaifeng Jiang. "Income Inequality in the United States: Reflections on the Role of Corporations." Academy of Management Review 43, no. 1 (January 2018): 156–68. http://dx.doi.org/10.5465/amr.2016.0527.

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Borkowski, Susan C. "Factors motivating transfer pricing choices of Japanese and United States transnational corporations." Journal of International Accounting, Auditing and Taxation 6, no. 1 (January 1997): 25–47. http://dx.doi.org/10.1016/s1061-9518(97)90011-2.

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Journal articles on the topic 'United States. Bureau of Corporations'

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