UNASSIGNED: 6514 Background: @entity29982 is a potent @entity7821 inhibitor. In an ongoing phase-1/2 multi-center study, 108 @entity1 with @entity4018 ( @entity4018 ) have so far been accrued. We present updated interim results for 60 @entity1 who have completed a minimum of 3 cycles of treatment. Additional information for the entire study cohort will be presented at the meeting. METHODS: @entity1 with high/intermediate-risk @entity4018 were included. @entity29982 was administered orally once daily in 28-day cycles. Responses were assessed by International Working Group (IWG) criteria. RESULTS: Dose-limiting @entity137 were grade 3 hyperlipasemia and grade 3 @entity10 . The maximum tolerated dose was 300 mg/day. The study retention rate after a median of 6.4 months was 92%. About half of the @entity1 experienced a first-dose effect (transient lightheadedness and @entity551 ), which was self-limited and generally resolved within hours with rare recurrence. Grade 3/4 hematologic and non-hematologic adverse events were infrequent with the exception of @entity882 , which occurred in approximately 25% of @entity1 . Forty-two @entity1 were evaluable for @entity417 response per IWG criteria (Blood 2006;108:1497) and 33 were red cell transfusion-dependent. In the latter group, @entity417 response required a transfusion-free period of >= 12 weeks, while on protocol drug therapy, and capped by a hemoglobin level of >= 8 g/dL. Accordingly, the overall @entity417 response rate was 50% and 58% in transfusion-dependent @entity1 . The median duration of @entity417 response was 20 weeks (range 12-54) and only 2 (11%) of the 19 @entity1 who achieved transfusion-independency required single episodes of PRBC transfusions. Responses in @entity417 were not affected by leukocyte count (p=0.39), platelet count (p=0.35), circulating blast count (p=0.35), circulating CD34 cell count (p=0.78), karyotype (p=0.67) or @entity4016 V617F mutational status (p=0.17). Spleen response rate by IWG criteria was approximately 45% whereas the majority of @entity1 experienced resolution of constitutional symptoms including @entity111 , night sweats and @entity158 . CONCLUSIONS: @entity29982 is unique among JAK inhibitors because of its ability to induce durable @entity417 responses in a significant number of @entity1 with @entity4018 .

Safety and efficacy of @entity29982 , a @entity7821 inhibitor, for the treatment of XXXX .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity417 :: ('MESH:D000740', 'Disease') :: ['anemia'] @entity7821 :: ('3716;3717', 'Gene') :: ['JAK-1/2'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity4016 :: ('3717', 'Gene') :: ['JAK2'] @entity551 :: ('MESH:D007022', 'Disease') :: ['hypotension'] @entity111 :: ('MESH:D011537', 'Disease') :: ['pruritus'] @entity4018 :: ('MESH:D055728', 'Disease') :: ['myelofibrosis', 'MF'] @entity158 :: ('MESH:D010146', 'Disease') :: ['bone pain'] @entity10 :: ('MESH:D006261', 'Disease') :: ['headache'] @entity29982 :: ('MESH:C546012', 'Chemical') :: ['CYT387']
@entity4018 :: (MESH:D055728,Disease) :: ['myelofibrosis']
