In the primary analysis, a higher proportion of patients receiving ruxolitinib vs the best available therapy achieved the composite primary endpoint of hematocrit control and ≥35% reduction in spleen volume from baseline at Week 32 (20.9% vs 0.9%, P<0.001).22 Higher proportions of patients receiving ruxolitinib also achieved individual components of the primary endpoint (hematocrit control, 60.0% vs 19.6%; ≥35% reduction in spleen volume from baseline, 38.2% vs 0.9%)22 and complete hematologic response (23.6% vs 8.9%, P=0.003)22 at Week 32 (Table 1). A post hoc analysis demonstrated that the degree of splenomegaly at baseline did not influence the achievement of hematocrit control or spleen size reduction with ruxolitinib treatment.106 Data also suggest that ruxolitinib conferred benefits in patients who did not meet the primary study endpoint. In patients who did not achieve hematocrit control at Week 32, ruxolitinib prolonged the median time to subsequent phlebotomy eligibility compared with the best available therapy (52 weeks vs 21 weeks, respectively).107

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(To view a larger version of Table 1, click here.)

A total of 96 patients (85.7%) initially randomized to receive the best available therapy crossed over to the ruxolitinib arm because of lack of efficacy; most did so at or soon after the Week 32 visit.22 After cross over to ruxolitinib, a greater proportion of patients achieved ≥35% reduction in spleen size (crossover, 38.5%; best available therapy during randomized treatment, 1.8%), and phlebotomy treatment rates were lower (crossover, 38.5/100 patient-years; best available therapy during randomized treatment, 196.8/100 patient-years).108

A preplanned analysis of RESPONSE conducted 80 weeks after the last patient received his/her first dose demonstrated a durable response with ruxolitinib. This analysis indicated that of the 23 patients randomized to ruxolitinib who achieved the primary endpoint response at Week 32, only one patient lost the response.109 The primary endpoint components were also durable; the probability of maintaining hematocrit control without phlebotomy was 89%, and no patients who achieved ≥35% spleen volume reduction at Week 32 lost their response.109 Furthermore, patients who achieved a complete hematologic response in the primary analysis had a 69% probability of maintaining this response for ≥80 weeks after their initial response.109

Ruxolitinib treatment has also been associated with a decrease in JAK2V617F allele burden in patients with PV. In RESPONSE, the mean JAK2V617F allele burden changes from baseline in the ruxolitinib arm were −12.2% and −34.7% at Weeks 32 and 112, respectively.22 In contrast, patients randomized to receive the best available therapy had a mean 1.2% increase in JAK2V617F allele burden at Week 32.22 A single-center study of 22 patients with PV (n=11) or ET (n=11) reported mean changes in JAK2V617F allele burden of −19% and −28% after 36 months and 60 months of treatment with ruxolitinib, respectively.110

Patient-reported outcomes

Patient-reported outcomes favored ruxolitinib over the best available therapy in Phase III RESPONSE trial, with consistent improvements in the MPN-SAF, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30, Pruritus Symptom Impact Scale, and Patient Global Impression of Change instruments, compared with little improvement or worsening observed with the best available therapy (Table 2).22 Notably, even patients who did not achieve hematocrit control with ruxolitinib at Week 32 reported a higher degree of symptom improvement as evaluated by the MPN-SAF compared with patients who received the best available therapy (38% vs 4%, respectively).107

The randomized, multicenter, double-blind, double-dummy, Phase IIIb RELIEF trial was conducted in patients receiving a stable dose of hydroxyurea who were generally well controlled but reported disease-associated symptoms, comparing the change in PV-related symptom burden in patients continuing their hydroxyurea therapy with those switching to ruxolitinib treatment.111 There was a nonsignificant trend toward a greater improvement in the MPN-SAF cytokine cluster TSS (TSS-C) with ruxolitinib compared with hydroxyurea (proportion of patients achieving ≥50% reduction from baseline in TSS-C at Week 16: 43.4% vs 29.6%, respectively; primary endpoint).111 Additionally, there was a nonsignificant trend toward improvement in individual TSS-C symptoms with ruxolitinib compared with continued hydroxyurea in the RELIEF trial.111