Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial

Abstract

RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7% vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hematocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea-resistant or intolerant patients with polycythemia vera. This trial was registered at clinicaltrials.gov identifier: 01243944.

Trial registration: ClinicalTrials.gov NCT01243944.

Figure 1.

Patient disposition. *One patient withdrew consent and was not treated on study; initial best available therapy included hydroxyurea (n=66), interferon/pegylated interferon (n=13), anagrelide (n=8), immunomodulators (n=5), pipobroman (n=2), and observation (n=17). ^†2 patients who discontinued because of an adverse event died during follow-up.

Figure 2.

Durability of primary response with ruxolitinib treatment.

Figure 3.

Duration of hematocrit control with ruxolitinib treatment. *Duration of the absence of phlebotomy eligibility is defined as the time from first occurrence of absence of phlebotomy eligibility until the date of the first documented progression.

Figure 4.

Mean hematocrit levels (A), white blood cell counts (B), and platelet counts (C) over time. Includes all data points with >5 patients. For patients in the ruxolitinib crossover group, baseline represents the date of crossover to ruxolitinib. Ruxolitinib and best available therapy arm data are from the 80-week data cutoff; ruxolitinib crossover data are from the 48-week data cutoff. WBC: white blood cell.