Expand: a Phase 1b, Open-Label, Dose-Finding Study of Ruxolitinib in Patients with Myelofibrosis and Baseline Platelet Counts Between 50 × 109/L and 99 × 109/L

Abstract Abstract 177 Background: Ruxolitinib (rux) is a potent oral JAK1 and JAK2 inhibitor that has demonstrated superiority over traditional therapies for the treatment of myelofibrosis (MF). In the two phase 3 COMFORT studies, rux demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life. Although there has been considerable experience in patients (pts) who developed thrombocytopenia in the COMFORT studies, there has been limited experience in pts with baseline thrombocytopenia as those with platelet counts (PLTs) 28 days of treatment and are evaluable. 2 pts were nonevaluable: 1 pt discontinued at day 6 due to granulocytic sarcoma, and 1 pt took an incorrect dosage from day 1 to 7 but treatment is ongoing. Reported adverse events (AEs) were similar to those previously seen with rux. 7 pts experienced grade 3/4 AEs (only 2 anemia events were study-drug related), and 4 pts experienced serious AEs (Table). The majority of hemoglobin and absolute neutrophil count (ANC) abnormalities were grade 1 or 2. No pt had a grade 4 decrease in PLTs or ANC; 2 pts experienced a grade 4 decrease in hemoglobin. No pt discontinued due to anemia, neutropenia, or thrombocytopenia. No hemorrhagic events were observed. The lowest PLTs across all pts ranged from 29–96 × 109/L. No dose-limiting toxicities (DLTs) were observed. Reductions in spleen length were reported for all 12 evaluable pts and 1 ongoing nonevaluable pt. Splenomegaly completely resolved in 3 pts. Spleen length reductions were rapid and occurred within the first few weeks of therapy. Conclusions: In this study, no DLT has occurred with the first 3 dose levels in pts with PLTs 75–99 × 109/L or with the first dose level in pts with PLTs 50–74 × 109/L. Rux was generally well tolerated, similar to results reported in previous studies, and no pt has discontinued because of thrombocytopenia. The study is ongoing, and additional pts are being recruited for both strata. Pts are receiving dose levels approaching those approved for nonthrombocytopenic MF pts. Disclosures: Harrison: Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Gisslinger:Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; AOP Orphan Pharmaceuticals AG: Consultancy, Speakers Bureau. Miller:Novartis: Consultancy, Research Funding, Speakers Bureau, development of educational presentations Other; Incyte: development of educational presentations, development of educational presentations Other. Kiladjian:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Atienza:Novartis Pharmaceuticals Corporation: Employment. Stalbovskaya:Novartis Pharma AG: Employment, Equity Ownership. Sirulnik:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Al-Ali:Sanofi Aventis: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Novartis: Consultancy, Honoraria. McMullin:Novartis: Honoraria; Bristol-Myers Squibb: Honoraria; Shire: Honoraria. Verstovsek:Incyte Corporation: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees.