Ruxolitinib for the Treatment of Inadequately Controlled Polycythemia Vera without Splenomegaly: 156-Week Follow-up from the Phase 3 Response-2 Study

BACKGROUND Ruxolitinib (RUX), a potent Janus kinase (JAK)1/JAK2 inhibitor, is approved for hydroxyurea (HU)-resistant/-intolerant patients (pts) with polycythemia vera (PV) based on findings from the RESPONSE study (NCT01243944). RUX proved superior to best available therapy (BAT) in maintaining hematocrit (Hct) control without phlebotomy eligibility, normalizing blood cell count, reducing spleen volume, and improving symptoms in pts with PV with splenomegaly who are resistant to or intolerant of HU. RESPONSE-2 (NCT02038036) is a global, multicenter, open-label, phase 3 trial comparing RUX with BAT in HU-resistant or -intolerant pts with PV without splenomegaly. In the primary analysis at wk 28, RUX proved superior to BAT in controlling Hct without phlebotomy eligibility, normalizing blood cell count, and improving symptoms. Responses were durable at 80 wk of follow-up. Here we evaluate the long-term safety and efficacy of RUX after a follow-up of 156 wk. METHODS Patients were randomized 1:1 to RUX 10 mg twice daily or BAT; BAT patients could cross over to RUX starting at wk 28. The primary endpoint was Hct control at wk 28 (absence of phlebotomy eligibility [Hct >45% and ≥3% higher than baseline, or >48%] from wk 8 to 28, with ≤1 phlebotomy eligibility up to wk 8). The key secondary endpoint was complete hematologic remission (CHR; Hct control, white blood cell count