Results of a prospective, randomized, open-label phase 3 study of ruxolitinib (RUX) in polycythemia vera (PV) patients resistant to or intolerant of hydroxyurea (HU): the RESPONSE trial

Abstract

7026 Background: PV is a myeloproliferative neoplasm characterized by increased erythrocytosis, disease-related symptom burden (eg, pruritus), and risk of vascular events (thrombosis and/or hemorrhage). Maintaining hematocrit (HCT) control is a key therapeutic goal. RESPONSE is the first phase 3 study to evaluate a JAK inhibitor (RUX) in treating PV. Methods: Phlebotomy (PBT)-dependent patients (pts) with splenomegaly (> 450 cm3) and HU resistance/intolerance were randomized 1:1 to RUX 10 mg bid or best available therapy (BAT). The primary endpoint was the proportion of pts who achieved both HCT control without PBT from wk 8 to 32 (with ≤ 1 PBT from wk 0 to 8) and a ≥ 35% reduction in spleen volume (SV) from baseline (BL) by MRI at wk 32. Key secondary endpoints included the proportion of pts who maintained the primary response at wk 48 and the proportion of pts who achieved complete hematologic response (CHR) at wk 32. Other endpoints were duration of response, symptom improvement by MPN-SAF diary, and safety. BAT-treated pts could cross over to RUX from wk 32. The primary analysis occurred when all pts reached wk 48 or discontinued. Results: 110 and 112 pts were randomized to RUX and BAT, respectively (median exposure: RUX, 81 wk; BAT, 34 wk); 17 (15%) RUX and 108 (96%) BAT pts discontinued randomized treatment (96 crossed over to RUX). The primary endpoint was achieved in 21% of RUX vs 1% of BAT pts (P < .0001); 91% of RUX pts maintained their response at wk 48. Overall, 77% of RUX pts met ≥ 1 component of the primary endpoint: 60% of RUX and 20% of BAT pts achieved HCT control without PBT; 38% of RUX and 1% of BAT pts achieved a ≥ 35% SV reduction (median BL SV, 1195 cm3 in RUX and 1322 cm3 in BAT pts). CHR was achieved in 24% and 9% of RUX and BAT pts (P = .003); 49% vs 5% had a ≥ 50% improvement in MPN-SAF 14-item total symptom score at wk 32. During the first 32 wk, grade 3/4 anemia or thrombocytopenia occurred in 1.8% and 5.5% of RUX pts, respectively, vs 0% and 3.6% of BAT pts; thromboembolic events occurred in 1 RUX and 6 BAT pts. Conclusion: RUX was well tolerated and superior to BAT in controlling HCT without PBT and reducing SV. RUX was also effective in improving PV-associated symptoms. Clinical trial information: NCT01243944.