Literatura académica sobre el tema "First Philippine Holdings Corporation"

Title – UMW Holdings: sustaining a centennial corporation. Subject area – Strategic Management and Organization Theory and Design. Study level/applicability – Advanced undergraduate and MBA students taking courses in Strategic Management and Organization Theory and Design. Case overview – By the end of 2011, five years short of its centennial anniversary, UMW Holdings was one of the biggest corporations in Malaysia, registering revenues of RM13.5 billion (US$4.5 billion), and net profit after tax of RM1 billion (US$0.33 billion). By that time, it had 110 subsidiaries, operating in four core businesses of automotive assembly and distribution of Toyota lines of products, automotive components and lubricants original equipment manufacturing (OEM) and replacement equipment manufacturing (REM), heavy equipment, and oil and gas drilling service. In September 2011, the company had targeted its Toyota automotive business to contribute to 50 percent of its revenues, while the other 50 percent would come from its other three businesses, by the year 2015. However, as of the first quarter of 2012, Datuk Syed Hisham Syed Wazir, the Group CEO and his management team realized that, at 72 percent, the automotive business was still the main contributor to the Group ' s revenues. As the company ' s Toyota assembly operation was limited exclusively to the Malaysian market, plus in the face of greater competition within the automotive industries, the company needed to set strategies to achieve its 50:50 plan. The case stimulates discussion on strategy formulation of a mature corporation, involved in diversified business portfolio. Expected learning outcomes – Understanding the process of industry analysis, as well as the formulation and implementation of business-level and corporate strategies, enables case analysts to extend the concepts to many business situations. Supplementary materials – Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

This decision is the latest of several by arbitral bodies of the International Centre for Settlement of Investment Disputes (ICSID) addressing a claim by Amco Asia Corporation (Amco Asia) against respondent Republic of Indonesia. An ICSID tribunal (First Tribunal) in 1984 rendered an award on the merits in favor of claimant Amco Asia. In 1986 an “ad hoc committee” (Ad Hoc Committee) convened on Indonesia’s request pursuant to Article 52 of the ICSID Convention annulled the 1984 award on the grounds that, with respect to a principal holding, the tribunal had “manifestly exceeded its powers” and “failed to state reasons,” both being grounds for annulment specified in Article 52(1) of the Convention. The Ad Hoc Committee did not disturb certain other holdings of the tribunal. Claimant then resubmitted the dispute, and a second tribunal (Second Tribunal) was constituted pursuant to Article 52(6) of the Convention. The first task of the new tribunal was to determine which holdings of the previous bodies were res judicata and therefore could not be relitigated. The three-member ICSID Second Tribunal held: (1) that holdings of the First Tribunal that had not been annulled by the Ad Hoc Committee were res judicata; (2) that issues as to which the First Tribunal’s holdings had been annulled could be relitigated; and (3) that the Ad Hoc Committee’s reasoning, as distinct from its actual decision of annulment, was not binding on the Second Tribunal.

The history of mining enterprise has recently become an important growth industry in both African and British Commonwealth business history. A number of important multinational mining corporations have in recent years opened their archives on assimilated or restructured parent companies active in overseas enterprise in the first half of this century. In the following essay, Professor Dumett surveys the extensive holdings of the leading British gold mining company in West Africa, the Ashanti Goldfields Corporation.

The article analyzes the scientific views on the concepts of «legal entity» and «corporation» formed in different legal systems, indicating either the identity of these concepts, or their heterogeneity by deducing a number of common and distinct features. Determined that in the Anglo-American legal system, the corporation is seen as a collective term, which should be understood by business associations and nonbusiness capital entities created to meet social objectives. It is proved that in EU law the concept of «corporation» is not identical with that of a legal entity, although a considerable number of types of legal entities are proposed to be included in the list of legal entities. In the countries of the continental legal system (France, Germany, Switzerland, Russia, Ukraine, etc.) the term «corporation» is rarely used in the law. This concept is used mainly in literary sources. Corporations include: various types of companies (full and limited partnerships, joint stock companies and other companies, members of which are limited liability for the obligations of the company), business associations (groups, trade unions, holdings, etc.), cooperatives, leases and state-owned enterprises, as well as various non-economic unions and associations. The main difference between the range of legal entities in the Anglo-American and Continental legal families is that in the first case, the terms «legal entity» and «corporation» are correlated as interchangeable concepts, and in the other case, the possibility of correlation between the concepts of «legal entity» and «corporation» depends on the approach of the legislation of the country to the definition of their organizational and legal forms and the formation in the scientific circles of the criteria for their separation or integration into one or another concept, or the introduction of this concept into the existing legislation of the EU country with a clear list of organizational and legal forms. Therefore, every legal family has their own approaches to the concept of «corporation».

In conducting its business, the corporation stands in corporate ethics and involves many things are about human rights, labor standards or workers, and relationships with the corporate environment. Ideally corporate ethics also puts workers as one form of social responsibility to represent a healthy or not as a company. PT Alpen Food Industry (AFI), a subsidiary of Aice Group Holdings Pte.Ltd Singapore produces Aice ice cream. The company ran into many aspects of ethical and legal (the laws) violations. This paper will discuss ethical violations in the business practices of PT Alpen Food Industry and elaborate on the importance of corporate ethics as a business fence. Furthermore, this paper will be classified in several sub-discussions. First, the ethical dimension approach (ethical behavior) in the corporation. Second, the dynamics in corporate ethics and public relations PT Alpen Food Industry. Third, the unethical business practices of PT Alpen Food Industry. Fourth, provide recommendations on the importance of government regulatory sharpening involved in the business practices of PT Alpen Food Industry to encourage corporate ethics in accordance with the laws and ethical standards of corporate ethics.Keywords: corporate ethics, the laws, labor, industry, regulation ABSTRAKDalam menjalankan bisnisnya, perusahaan terikat dalam etika perusahaan dan melibatkan hal mengenai hak asasi manusia, standar tenaga kerja, dan hubungan dengan lingkungan perusahaan. Idealnya etika perusahaan juga menempatkan pekerja sebagai salah satu bentuk tanggung jawab sosial perusahaan. PT Alpen Food Industry (AFI), anak perusahaan Aice Group Holdings Pte.Ltd Singapura memproduksi es krim Aice mengalami beberapa aspek pelanggaran etika dan hukum (hukum) terutama dalam hal tenaga kerja. Makalah ini akan membahas pelanggaran etika dalam praktik bisnis PT Alpen Food Industry dan menguraikan pentingnya etika perusahaan sebagai pagar bisnis. Selanjutnya, makalah ini akan diklasifikasikan dalam beberapa sub-diskusi. Pertama, pendekatan dimensi etis (perilaku etis) dalam perusahaan. Kedua, dinamika etika perusahaan dan hubungan masyarakat PT Alpen Food Industry. Ketiga, praktik bisnis yang tidak etis dari PT Alpen Food Industry. Keempat, memberikan rekomendasi tentang pentingnya penajaman peraturan pemerintah yang terlibat dalam praktik bisnis PT Alpen Food Industry untuk mendorong etika perusahaan sesuai dengan hukum dan standar etika etika perusahaan.Kata kunci: etika perusahaan, hukum, ketenagakerjaan, industri, regulasi

The date pineapple (Ananas comosus var. comosus) was introduced to Hawaii is not known, but its presence was first recorded in 1813. When American missionaries first arrived in Hawaii in 1820, pineapple was found growing wild and in gardens and small plots. The pineapple canning industry began in Baltimore in the mid-1860s and used fruit imported from the Caribbean. The export-based Hawaii pineapple industry was developed by an entrepreneurial group of California migrants who arrived in Hawaii in 1898 and the well-connected James D. Dole who arrived in 1899. The first profitable lot of canned pineapples was produced by Dole’s Hawaiian Pineapple Company in 1903 and the industry grew rapidly from there. Difficulties encountered in production and processing as the industry grew included low yields resulting from severe iron chlorosis and the use of low plant populations, mealybug wilt that devastated whole fields, inadequate machinery that limited cannery capacity, and lack of or poorly developed markets for the industry’s canned fruit. The major production problems were solved by public- and industry-funded research and innovation in the field and in the cannery. An industry association and industry-funded cooperative marketing efforts, initially led by James Dole, helped to expand the market for canned pineapple. Industry innovations were many and included: selection of ‘Smooth Cayenne’ pineapple as the most productive cultivar with the best quality fruit for canning; identification of the cause of manganese-induced iron chlorosis and its control with biweekly iron sulphate sprays; the use of mulch paper and the mechanization of its application, which increased yields by more than 20 t·ha−1; and the invention of the Ginaca peeler–corer machine, which greatly sped cannery throughput. Nematodes were also a serious problem for the industry, which resulted in the discovery and development of nematicides in the 1930s. As a result, by 1930 Hawaii led the world in the production of canned pineapple and had the world’s largest canneries. Production and sale of canned pineapple fell sharply during the world depression that began in 1929. However, the formation of an industry cartel to control output and marketing of canned pineapple, aggressive industry-funded marketing programs, and rapid growth in the volume of canned juice after 1933 restored industry profitability. Although the industry supported the world’s largest pineapple breeding program from 1914 until 1986, no cultivars emerged that replaced ‘Smooth Cayenne’ for canning. The lack of success was attributed in part to the superiority of ‘Smooth Cayenne’ in the field and the cannery, but also to the difficulty in producing defect-free progeny from crosses between highly heterozygous parents that were self-incompatible. Production of canned pineapple peaked in 1957, but the stage was set for the decline of the Hawaii industry when Del Monte, one of Hawaii’s largest canners, established the Philippine Packing Corporation (PPC) in the Philippines in the 1930s. The expansion of the PPC after World War II, followed by the establishment of plantations and canneries by Castle and Cooke’s Dole division in the Philippines in 1964 and in Thailand in 1972, sped the decline. The decline occurred mainly because foreign-based canneries had labor costs approximately one-tenth those in Hawaii. As the Hawaii canneries closed, the industry gradually shifted to the production of fresh pineapples. During that transition, the pineapple breeding program of the Pineapple Research Institute of Hawaii produced the MD-2 pineapple cultivar, now the world’s pre-eminent fresh fruit cultivar. However, the first and major beneficiary of that cultivar was Costa Rica where Del Monte had established a fresh fruit plantation in the late 1970s. Dole Food Co. and Maui Gold Pineapple Co. continue to produce fresh pineapples in Hawaii, mostly for the local market. All of the canneries eventually closed, the last one on Maui in 2007.

Abstract Background: The growth factor receptor bound protein-2 (Grb2) is vital to tumor progression. Prexigebersen (BP1001) is a liposome-incorporated Grb2 antisense oligonucleotide that inhibits Grb2 expression. Grb2 inhibition suppresses cancer growth and survival. A Phase I/IB single center study (Ohanian, Lancet Haematol 2018) in relapsed/refractory AML patients (pts) demonstrated BP1001 safety up to 90 mg/m2 and demonstrated CR/CRi in 3/6 relapsed/refractory AML pts treated with BP1001 + low dose cytarabine (LDAC) in the Phase IB portion. Based on PK considerations, the recommended Phase II dose was 60 mg/m2. A phase II study was initiated to explore the clinical impact of BP1001 in untreated AML pts considered unsuitable for standard chemotherapy. Methods: This is a multi-center open-label, Phase II study in untreated AML pts to determine the safety and preliminary efficacy of BP1001 (given at 60 mg/m2 over 1-3 h twice weekly for a total of 8 doses over a 28-day cycle) in combination with LDAC (starting after the Day 4 dose, 20 mg twice daily for 10 days). Eligible pts were considered unsuitable for or refused intensive chemotherapy and had ECOG performance status of 0-2. Blood samples were taken on Days 1 and 11 to determine BP1001 plasma pharmacokinetics (PK). Results: A total of 25 pts (16 male: 64%) with a median age of 74 years (range, 51-86 years) was treated with at least 1 cycle of BP1001 + LDAC. Sixty-eight percent (17/25) had secondary AML evolved from MDS (n=13) or MPN (n=3) or prior chemotherapy/radiotherapy (n=1). The majority (64%) had adverse-risk (ELN classification); 36% were intermediate-risk. Infusional reactions (IR) (rigors, fevers, or chills) were observed in 20% of pts when the infusion rate was 1 h. IR were mild, controlled with supportive measures, and were not observed when the infusion rate was 2 h. Other AE's were generally consistent with those expected with LDAC and/or AML, including fatigue (64%), diarrhea (24%), neutropenic fever (24%), and pneumonia (20%). The most frequent SAEs were pneumonia (20%) and neutropenic fever (24%). Four pts died within 30 days of treatment (between days 20-27), all of AML-related complications (including intracranial hemorrhage, pneumonia, septic shock, and splenic rupture). Ten pts had documented progressive disease. Two pts withdrew consent after 1 cycle of treatment. Evaluability of efficacy was defined as: receipt of at least 4 cycles of therapy, PD, or CR/CRi prior to 4 cycles. PK data revealed that the Time of maximal observed concentration (Tmax), the mean terminal elimination half-life (t1/2), and the area under the curve from zero to the last quantifiable concentration (AUC(last)) for BP1001 were similar between Days 1 and 11. Tmax of BP1001 was 1.9 vs 2.3 h (day 1 vs 11); t1/2 was 5.2 vs 5.7 h; AUC(last) was 308 vs 275 h*ng/mL. Response: Among 17 fully evaluable pts, 7 pts (41%) demonstrated bone marrow blast reduction, including 5 (29%) who achieved a CR (n=3), CRi (n=1), or morphologic leukemia free state (n=1). Two additional pts demonstrated a ≥50% reduction of bone marrow blasts (from 20% to 9% and from 71% to 8%), including 1 with hematologic improvement of the absolute neutrophil count. The median overall survival (OS) was 5.2 months (range, 0.6-15.2) for all patients. For evaluable patients, the median OS was 6.3 months (0.8-15.2 months). The CRs included: a 74-year old female who achieved CR after 2 cycles of therapy and then received 2 additional cycles followed by a matched-sibling allogeneic transplant. She remained in CR for 10 months before first relapse. A 73-year old female, with AML transformed from MDS, benefited from therapy despite refusal of blood products due to religious objections. Her hemoglobin declined to 4.0 g/dL during therapy but recovered to as high as 9.9 g/dL once in CR after 4 cycles. An 86-year old male achieved CR after 4 cycles of therapy and maintained CR for 3 months before relapse. Conclusions: BP1001 has been safely administered to 25 pts with untreated AML, who were considered unsuitable for standard chemotherapy. Efficacy data are encouraging in a challenging population in which the majority of pts had secondary AML or adverse-risk AML, and compares favorably to the reported CR/CRi/CRp rate with LDAC of 7-13% (Heiblig, Mediterr J Hematol 2016; Kantarjian, J Clin Oncol 2012; Döhner, Blood 2014). A protocol amendment made to optimize BP1001 administration with LDAC and to add a decitabine combination arm is in place. Disclosures Lin: Jazz Pharmaceuticals: Honoraria. Ritchie:Incyte: Consultancy, Speakers Bureau; Astellas Pharma: Research Funding; NS Pharma: Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau; Bristol-Myers Squibb: Research Funding; Pfizer: Consultancy, Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau. Craig:Celgene: Research Funding; Novartis: Research Funding; Actinium Pharmaceuticals: Research Funding. Agrawal:Incyte: Speakers Bureau. Pemmaraju:Affymetrix: Research Funding; plexxikon: Research Funding; daiichi sankyo: Research Funding; SagerStrong Foundation: Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; abbvie: Research Funding; cellectis: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding. Tari Ashizawa:Bio-Path Holdings, Inc.: Employment, Equity Ownership, Patents & Royalties. Hahne:Bio-Path Holdings, Inc.: Employment. Cortes:Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Arog: Research Funding. Roboz:Orsenix: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Cellectis: Research Funding; Roche/Genentech: Consultancy; Novartis: Consultancy; Janssen Pharmaceuticals: Consultancy; Aphivena Therapeutics: Consultancy; Celltrion: Consultancy; Otsuka: Consultancy; Sandoz: Consultancy; Orsenix: Consultancy; Roche/Genentech: Consultancy; Celgene Corporation: Consultancy; Astex Pharmaceuticals: Consultancy; AbbVie: Consultancy; Daiichi Sankyo: Consultancy; Cellectis: Research Funding; Aphivena Therapeutics: Consultancy; Janssen Pharmaceuticals: Consultancy; Novartis: Consultancy; Otsuka: Consultancy; Pfizer: Consultancy; Jazz Pharmaceuticals: Consultancy; Eisai: Consultancy; Eisai: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Pfizer: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy; Bayer: Consultancy; Celltrion: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy.

Abstract Introduction: Cytogenetic abnormalities occur frequently in patients with myelofibrosis (MF) and carry significant prognostic value. A variety of cytogenetic abnormalities have been reported with variable incidence. While the prognostic significance of more common cytogenetic abnormalities is well documented, the prognostic significance of less common abnormalities are difficult to discern due to limiting cohort size. Further, the specific phenotype associated with various cytogenetic abnormalities is less clear. We reviewed our institutional experience in an effort to describe the spectrum of chromosomal abnormalities, assess their correlation with clinical features, and validate their prognostic impact in a cohort of MF patients. Methods: This was a single institution, retrospective study of all patients with a diagnosis of MF who were seen at our center between 2/2001 - 6/2016.We reviewed cases of myelofibrosis in the Moffitt Cancer Center database. Definitions of primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia vera myelofibrosis (post-PV MF) were according to World Health Organization 2016 criteria and the International Working Group for Myeloproliferative Neoplasms, Research and Treatment, respectively. Cytogenetic analysis was documented with preference to date of diagnosis. Overall survival was measured from time of cytogenetic analysis. Results: We identified 312 eligible. Cytogenetic data were available in 278 of 312 (89%) patients. The cohort was 59% male with a median age of 70 years at time of first presentation. PMF comprised 76% of cases with post-PV MF and post-ET MF accounting for 9% and 15% of cases respectively. Cytogenetic analysis was performed within 3 months of diagnosis in 63% and over a year after diagnosis in 24% of patients. Cytogenetic spectrum and frequency is shown in Figure 1. Normal diploid karyotype was present in 55%. The most common cytogenetic abnormality was a deletion of the long arm of chromosome 20 (del 20q), occurring in 39 (14%) cases. Del 20q occurred as an isolated abnormality in 26/39 cases. When occurring in conjunction with other structural abnormalities, it was most often associated with trisomy 9 (6/39). A deletion of the long arm of chromosome 13 (del 13q) was the second most common chromosomal aberration, occurring in 26 (9%) of cases and usually presenting as the sole abnormality (15/26). An extra copy of chromosome 8 (trisomy 8) occurred in 21 (8%) cases and often occurred in conjunction with other cytogenetic abnormalities (11/21). Less common cytogenetic abnormalities included trisomy 9, deletion 7q and deletion 5q, occurring in less than 4% of cases. Monosomal and complex karyotypes accounted for 10% and 8.3% of cytogenetics, respectively. We then assessed relationships between cytogenetic abnormalities and clinical and pathologic features. Del20q was associated with a lower IPSS score (r = -0.18, p = 0.0006). Deletion 13q was associated with older age at presentation (r = 0.14, p = 0.007). Prevalence of trisomy 8 was highest in post-polycythemia vera myelofibrosis (r = 0.14, p = 0.03) and associated with increased peripheral blast percentage (r = 0.16, p < 0.0001). Deletion 5q was associated with decreased hemoglobin (r = -0.13, p = 0.04), transfusion dependence (r = 0.20, p = 0.0009) and conversion to blast phase (r = 0.23, p = 0.0001). Patients with del 20q, del 13q, and trisomy 9 had median overall survival (OS) comparable to patients with a normal karyotype (45 vs 54 months, respectively, p = 0.69). Patients with unfavorable cytogenetic profiles (del 5q, trisomy 8, and chromosome 17 abnormalities) had significantly worse OS when compared to patients with normal diploid karyotype (20 vs 54 months, p = 0.0002) (figure 2). In multivariate regression analysis, controlling for DIPSS, deletion 5q (HR: 0.34 [0.15-0.78]; p = 0.01) and trisomy 8 (HR: 0.35 [0.17-0.73]; p = 0.005) were significantly associated with inferior overall survival. Conclusions: Cytogenetic abnormalities in myelofibrosis provide significant prognostic discrimination in patients with myelofibrosis. Our findings validate the prognostic value of cytogenetics and raise possible heretofore unrecognized clinical associations. Disclosures Lancet: Novartis: Consultancy; Biopath Holdings: Consultancy; Karyopharm: Consultancy; Boehringer-Ingelheim: Consultancy; Quantum First: Consultancy; ERYtech: Consultancy; Pfizer: Research Funding; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Kalo Bios: Consultancy; Baxalta: Consultancy; Amgen: Consultancy. Sweet:Incyte Corporation: Research Funding; Pfizer: Speakers Bureau; Karyopharm: Honoraria, Research Funding; Ariad: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Komrokji:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Speakers Bureau.

Abstract Background: Prognostication in MF has historically been based on age, symptoms and hematologic features at presentation. Newer models include cytogenetic and genomic data given their independent prognostic value. In 2014, two prognostic models incorporating gene mutation data were proposed: a "mutation enhanced" IPSS (MIPSS) and a genetics-based prognostic scoring system (GPSS) model; the former using mutation data to enrich standard prognostic inputs, while the latter eschewed classic prognostic inputs for a score comprised solely of cytogenetics, mutation data, and age (Vannucchi, Blood, 2014 and Tefferi, Blood, 2014). In this study, we aimed to validate these risk models as well as propose age-independent models to better capture disease-specific prognosis. Methods: This was a single institution, retrospective study of confirmed MF patients seen between 2/2001 and 6/2016. Definitions of primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia vera myelofibrosis (post-PV MF) were according to World Health Organization 2016 criteria and the International Working Group for Myeloproliferative Neoplasms, Research and Treatment, respectively. Mutation and cytogenetic data were assessed from review of electronic medical record. Prognostic scores were calculated on first presentation to our facility. Survival curves were generated using Kaplan-Meier method and compared using the log-rank test. Results: We identified 103 and 97 patients with available data to calculate MIPSS and GPSS scores respectively. The cohorts were 60% male, with median age 72 years at presentation. The majority of patients had a diagnosis of PMF (80%), with a small component of post-ET MF (13%) and post-PV MF (7%). Assigning scores based on MIPSS, 4% of patients were low-risk (LR), 8% intermediate-1 (IR1), 60% intermediate-2 (IR2), and 28% high-risk (HR). The model successfully differentiated between IR2 and HR with median overall survival (OS) 134 and 26 months, respectively (p = 0.0001) (figure 1A). No significant difference in OS was seen between LR/IR1 groups and IR2 (p = 0.58). Using GPSS, 1% of patients were classified as LR, 13% IR1, 25% IR2, and 61% HR. GPSS performed well in delineating between HR and intermediate risk (combined IR1 and IR2) (median OS 44 vs 134 mo, p = 0.02); however it did not distinguish HR from IR2 (p = 0.09) nor between IR1 and IR2 (p = 0.71) (figure 1B). To more specifically assess disease-specific prognosis and better divide risk scores among our patient population, new models were created. Given that age is a negative risk factor for OS independent of disease state, this input was removed. First, an age-independent MIPSS score was created with four risk groups defined: LR (score 0-0.5), IR1 (score 1-1.5), IR2 (2-3), and HR (score 3.5+). Fifteen percent of patients were classified as LR, 32% IR1, 48% IR2, and 6% HR. This system distinguished significantly between IR2 and HR (median OS 98.0 vs 13.5 mo, p = 0.006), while providing improved differentiation between IR1 and IR2 risk groups (median OS not reached vs. 98 months, p = 0.09) (figure 1C). Next, we aimed to create a truly disease-specific model based on the GPSS. Age was omitted and the impact of SRSF2 mutation was enhanced from 1 point to 1.5 points given its greater weighted impact on OS compared to ASXL1 mutation in our database. Values for other inputs remained consistent with GPSS. Using cytogenetic information (CY) and mutation data (M) as the sole inputs a CYM score was created. This yielded four risk groups defined as LR (0 points), IR1 (1-2.5 points), IR2 (3-5 points) and HR (5.5+ points). Seven percent of patients were classified as LR, 28% IR1, 56% IR2, and 9% HR. This model differentiated between IR2 disease and HR disease effectively (median OS 98 vs 15.2 mo., p < 0.0001). No significant difference was observed between IR1 and IR2 disease (figure 1D). Conclusion: Using previously proposed molecular-based models, we were able to validate their utility in the setting of advanced disease; however, insufficient capture of lower risk categories impaired its validity in that setting. We propose age-independent models to better characterize disease-specific risk in an effort to identify patients who many benefit from allogeneic stem cell transplant and/or clinical trial referral. These models merit testing in larger cohorts with longer follow-up to determine their clinical validity. Disclosures Lancet: Celgene: Consultancy, Research Funding; Amgen: Consultancy; Seattle Genetics: Consultancy; Quantum First: Consultancy; Biopath Holdings: Consultancy; Baxalta: Consultancy; Pfizer: Research Funding; Kalo Bios: Consultancy; Karyopharm: Consultancy; Jazz Pharmaceuticals: Consultancy; ERYtech: Consultancy; Boehringer-Ingelheim: Consultancy; Novartis: Consultancy. Sweet:Pfizer: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau; Incyte Corporation: Research Funding; Karyopharm: Honoraria, Research Funding. Komrokji:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Speakers Bureau.

Background Anemia is common in patients (pts) with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF). Furthermore, anemia is an on-target effect of therapeutic Janus kinase 2 (JAK2) inhibition, and may be the most frequent cause of ruxolitinib (rux) discontinuation (d/c) in clinical practice (Kuykendall, Ann Hematol 2018). Current therapies for anemia of MF (erythropoietin and analogs, danazol, IMiDs®) are unsatisfactory. Sotatercept (ACE-011) is a first-in-class, activin receptor type IIA ligand trap that may improve anemia by sequestering stromal transforming growth factor beta superfamily ligands that suppress terminal erythropoiesis (Iancu-Rubin, Exp Hematol 2013). Methods This is a phase 2, investigator-initiated, open-label, single institution study of sotatercept, administered subcutaneously every 3 weeks, in 2 cohorts of anemic pts (Hgb &lt;10 g/dl on every determination for 12 weeks (wks) or transfusion-dependent (TD) per IWG-MRT criteria (Tefferi, Blood 2013)) with MF: as a single agent, and in combination with a stable dose of rux. Pts on rux must have been on rux for ≥6 months with a stable dose for ≥8 weeks, and receive sotatercept at a dose of 0.75 mg/kg. Monotherapy pts receive either 0.75 or 1 mg/kg of sotatercept. In both cohorts, anemia response is defined as achievement of transfusion independence (TI) in TD pts, and an increase in Hgb level from baseline of ≥1.5 g/dl sustained for ≥12 wks in non-TD pts (Gale, Leuk Res 2011). Pts must have received ≥5 cycles of sotatercept to be response-evaluable. Results A total of 53 pts have been treated; one pt received only 0.3 mg/kg of sotatercept and is not considered further. Thirty one pts received sotatercept alone and 21 in combination with rux. Baseline characteristics appear in Table 1, panel A. Sixteen TD and 15 non-TD pts received sotatercept alone for a median of 5 (1-67) cycles. Thirteen pts received 0.75 mg/kg and 18, 1 mg/kg. Seven of 24 (29%) evaluable pts responded. Of these, 4 were anemia responses; 3 TD pts achieved TI. Five responses occurred at the 0.75 mg/kg dose, and 2 at the 1 mg/kg dose. Median time to response (TTR) was 21 (1-22) days and median duration of response (DOR) 13 (3.9-56.4) months. Seven pts (22.6%) received &lt;5 cycles and were not response-evaluable: 2 proceeded to stem cell transplant (SCT), 2 had logistical (travel) issues, and 1 each d/ced sotatercept because of hypertension (HTN), unrelated medical problems and pt decision. Three pts continue on study. Reasons for d/c included no response (11), progressive MF (6), SCT (3), travel logistics (3), patient decision (2), hypertension (1), unrelated medical complications (1) and transformation to AML (1). The combination cohort comprised 15 non-TD pts and 6 TD pts. The median number of cycles was 8 (2-43). Five of 17 (29%) evaluable pts in the combination cohort responded, all non-TD pts. Median TTR was 14 (7-147) days and median DOR 34.6 (3.1-47.9) months. Four pts (19%) received &lt;5 cycles and were not response-evaluable, 1 each due to MF progression, loss of insurance, SCT and pt decision. Five pts remain on study. Reasons for d/c included no response (6), SCT (4), progressive MF (2), travel logistics (2), loss of insurance (1) and pt decision (1). Several non-response-evaluable pts in both cohorts achieved ≥1.5 g/dl increments in Hgb from baseline that were not sustained for ≥12 wks because of early d/c of sotatercept. An additional pt in the combination cohort required a rux dose increase, leading to failure to sustain a ≥1.5 g/dl Hgb improvement. Across both cohorts, several responding pts required multiple protocol-specified drug holidays because of Hgb levels ≥11.5 g/dl, with resumption of sotatercept once Hgb was &lt;11 g/dl. Sotatercept was well-tolerated (Table 1, panel B). Grade 3 adverse events possibly related to sotatercept were HTN (n=7), limb (bone/muscle/joint) pain (n=3) and headache (1). Conclusions Sotatercept is safe and effective against anemia of MPN-associated MF, both in non-TD and TD pts, with a response rate of 29% both when used alone and in conjunction with a stable dose of rux. A total of 60 pts are planned to be treated on this trial (NCT01712308). Disclosures Bose: Blueprint Medicines Corporation: Honoraria, Research Funding; NS Pharma: Research Funding; Constellation Pharmaceuticals: Research Funding; Astellas Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene Corporation: Honoraria, Research Funding; CTI BioPharma: Honoraria, Research Funding; Promedior, Inc.: Research Funding; Kartos Therapeutics: Honoraria, Research Funding. Pemmaraju:Samus Therapeutics: Research Funding; AbbVie: Honoraria, Research Funding; MustangBio: Honoraria; SagerStrong Foundation: Other: Grant Support; Roche Diagnostics: Honoraria; Pacylex Pharmaceuticals: Consultancy; Plexxikon: Research Funding; Daiichi Sankyo: Research Funding; Stemline Therapeutics: Honoraria, Research Funding; Celgene: Honoraria; Incyte Corporation: Honoraria; Cellectis: Research Funding; Blueprint Medicines: Honoraria; Affymetrix: Other: Grant Support, Research Funding; Novartis: Honoraria, Research Funding; LFB Biotechnologies: Honoraria; DAVA Oncology: Honoraria. Daver:Fate Therapeutics: Research Funding; Bristol-Myers Squibb: 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; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; ImmunoGen: Research Funding; Novartis: 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; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: 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. Jabbour:BMS: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding. Kadia:Astellas: Research Funding; Pulmotec: Research Funding; Incyte: Research Funding; Ascentage: Research Funding; JAZZ: Honoraria, Research Funding; Cyclacel: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Cellenkos: Research Funding; Genentech: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria; Abbvie: Honoraria, Research Funding; Astra Zeneca: Research Funding. Andreeff:Daiichi-Sankyo; Jazz Pharmaceuticals; Celgene; Amgen; AstraZeneca; 6 Dimensions Capital: Consultancy; Amgen: Research Funding; Daiichi-Sankyo; Breast Cancer Research Foundation; CPRIT; NIH/NCI; Amgen; AstraZeneca: Research Funding; Centre for Drug Research & Development; Cancer UK; NCI-CTEP; German Research Council; Leukemia Lymphoma Foundation (LLS); NCI-RDCRN (Rare Disease Clin Network); CLL Founcdation; BioLineRx; SentiBio; Aptose Biosciences, Inc: Membership on an entity's Board of Directors or advisory committees. Cortes:Bristol-Myers Squibb: Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sun Pharma: Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Telios: Research Funding; Astellas: Research Funding; Amphivena Therapeutics: Research Funding; Arog: Research Funding; BiolineRx: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Research Funding; Immunogen: Research Funding; Novartis: Consultancy, Research Funding. Jain:BMS: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aprea Therapeutics: Research Funding; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding. Borthakur:Nkarta Therapeutics: Consultancy; Treadwell Therapeutics: Consultancy; PTC Therapeutics: Research Funding; Jannsen: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Polaris: Research Funding; Xbiotech USA: Research Funding; Oncoceutics: Research Funding; Curio Science LLC: Consultancy; FTC Therapeutics: Consultancy; Argenx: Consultancy; PTC Therapeutics: Consultancy; BioLine Rx: Consultancy; BioTherix: Consultancy; Cyclacel: Research Funding; GSK: Research Funding; BioLine Rx: Research Funding; BMS: Research Funding; AstraZeneca: Research Funding. Alvarado:Sun Pharma: Research Funding; Astex Pharmaceuticals: Research Funding; MEI Pharma: Research Funding; Daiichi-Sankyo: Research Funding; Tolero Pharmaceuticals: Research Funding; FibroGen: Research Funding; Jazz Pharmaceuticals: Research Funding; BerGenBio ASA: Research Funding. Huynh-Lu:Incyte Corporation: Speakers Bureau. Nguyen-Cao:Incyte Corporation: Speakers Bureau. Garcia-Manero:Acceleron Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy; Novartis: Research Funding; Onconova: Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; AbbVie: Honoraria, Research Funding; H3 Biomedicine: Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amphivena Therapeutics: Research Funding. Kantarjian:Oxford Biomedical: Honoraria; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Delta Fly: Honoraria; Janssen: Honoraria; Ascentage: Research Funding; BioAscend: Honoraria; Amgen: Honoraria, Research Funding; Aptitute Health: Honoraria; Immunogen: Research Funding; Jazz: Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; BMS: Research Funding; Adaptive biotechnologies: Honoraria; Abbvie: Honoraria, Research Funding. Verstovsek:Sierra Oncology: Consultancy, Research Funding; Gilead: Research Funding; Celgene: Consultancy, Research Funding; CTI Biopharma Corp: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Novartis: Consultancy, Research Funding; AstraZeneca: Research Funding; ItalPharma: Research Funding; Protagonist Therapeutics: Research Funding; PharmaEssentia: Research Funding; Incyte Corporation: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding.