T L Lasho

6514 Background: CYT387 is a potent JAK-1/2 inhibitor. In an ongoing phase-1/2 multi-center study, 108 patients with myelofibrosis (MF) have so far been accrued. We present updated interim results for 60 patients who have completed a minimum of 3 cycles of treatment. Additional information for the entire study cohort will be presented at the meeting. Methods: Patients with high/intermediate-risk MF were included. CYT387 was administered orally once daily in 28-day cycles. Responses were assessed by International Working Group (IWG) criteria. Results: Dose-limiting toxicities were grade 3 hyperlipasemia and grade 3 headache. 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 patients experienced a first-dose effect (transient lightheadedness and hypotension), 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 thrombocytopenia, which occurred in approximately 25% of patients. Forty-two patients were evaluable for anemia response per IWG criteria (Blood 2006;108:1497) and 33 were red cell transfusion-dependent. In the latter group, anemia 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 anemia response rate was 50% and 58% in transfusion-dependent patients. The median duration of anemia response was 20 weeks (range 12-54) and only 2 (11%) of the 19 patients who achieved transfusion-independency required single episodes of PRBC transfusions. Responses in anemia 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 JAK2V617F mutational status (p=0.17). Spleen response rate by IWG criteria was approximately 45% whereas the majority of patients experienced resolution of constitutional symptoms including pruritus, night sweats and bone pain. Conclusions: CYT387 is unique among JAK inhibitors because of its ability to induce durable anemia responses in a significant number of patients with myelofibrosis.

Correction to: Blood Cancer Journal (2015) 4, e270; doi:10.1038/bcj.2014.90; published online 2 January 2015 Since publication, the publishers have identified that this article was incorrectly placed in volume 4. The article belongs in volume 5. The publishers would like to apologise for any inconvenience caused.