Inhibitor, in Patients With Advanced Polycythemia Vera Who Are Refractory or Intolerant to Hydroxyurea

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with somatic gain-of-function mutations of Janus kinase-2 (JAK2). Therapeutic options are limited in patients with advanced disease. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is active in preclinical models of PV. The long-term efficacy and safety of ruxolitinib in patients with advanced PV who are refractory or intoler-ant to hydroxyurea were studied in a phase 2 trial. METHODS: Response was assessed using modified European LeukemiaNet criteria, which included a reduction in hematocrit to <45 % without phlebotomy, resolution of palpable splenomegaly, normalization of white blood cell and platelet counts, and reduction in PV-associated symptoms. RESULTS: Thirty-four patients received ruxolitinib for a median of 152 weeks (range, 31 weeks-177 weeks) or 35.0 months (range, 7.1 months-40.7 months). Hematocrit <45 % without phlebotomy was achieved in 97 % of patients by week 24.Only 1 patient required a phlebotomy after week 4. Among patients with palpable splenomegaly at baseline, 44 % and 63%, respectively, achieved nonpalpable spleen measurements at weeks 24 and 144. Clinically meaningful improve-ments in pruritus, night sweats, and bone pain were observedwithin 4weeks of the initiation of therapy andmaintainedwith continued treat-ment. Ruxolitinib treatment also reduced elevated levels of inflammatory cytokines and granulocyte activation. Thrombocytopenia and anemia were the most common adverse events. Thrombocytopenia ofgrade 3 or anemia ofgrade 3 (according to National Cancer Insti-tute Common Terminology Criteria for Adverse Events,version 3.0) occurred in 3 patients each (9%) (1 patient had both) andwere managed with dose modification. CONCLUSIONS: Ruxolitinib was generally well tolerated and provided rapid and durable clinical benefits i