Ruxolitinib for the treatment of inadequately controlled polycythemia vera without splenomegaly: 80-week follow-up from the RESPONSE-2 trial

Martin Griesshammer,Guray Saydam,Paola Guglielmelli,Francesco Passamonti,Giulia Benevolo,Julian Perez Ronco,Francesca Palandri,Serdar Sivgin,Mahmudul Khan,Miklos Egyed,Jeannie Callum,Timothy Devos,Caroline Bensasson

doi:10.1007/s00277-018-3365-y

Abstract

RESPONSE-2 is a phase 3 study comparing the efficacy and safety of ruxolitinib with the best available therapy (BAT) in hydroxyurea-resistant/hydroxyurea-intolerant polycythemia vera (PV) patients without palpable splenomegaly. This analysis evaluated the durability of the efficacy and safety of ruxolitinib after patients completed the visit at week 80 or discontinued the study. Endpoints included proportion of patients achieving hematocrit control (< 45%), proportion of patients achieving complete hematologic remission (CHR) at week 28, and the durability of hematocrit control and CHR. At the time of analysis, 93% (69/74) of patients randomized to ruxolitinib were receiving ruxolitinib; while in the BAT arm, 77% (58/75) of patients crossed over to ruxolitinib after week 28. No patient remained on BAT by week 80. Among patients who achieved a hematocrit response at week 28, the probability of maintaining response up to week 80 was 78% in the ruxolitinib arm. At week 80, durable CHR was achieved in 18 patients (24%) in the ruxolitinib arm versus 2 patients (3%) in the BAT arm. The safety profile of ruxolitinib was consistent with previous reports. These data support that ruxolitinib treatment should be considered also as a standard of care for hydroxyurea-resistant/hydroxyurea-intolerant PV patients without palpable splenomegaly.

Highlights

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by an abnormal increase in red blood cell mass due to an activating mutation in the Janus kinase 2 (JAK2) gene [1]
The results from the Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) study demonstrated that controlling the hematocrit (HCT) level below 45% was associated with a fourfold reduction in the rates of major thrombotic events and cardiovascular deaths [8]
Patients were eligible if they had PV according to WHO criteria, were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, had no palpable splenomegaly, had no previous treatment with JAK inhibitors, and were phlebotomy-dependent

Summary

Introduction

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by an abnormal increase in red blood cell mass due to an activating mutation in the Janus kinase 2 (JAK2) gene [1]. 40% of patients with PV present with an increase in white blood cell (WBC) and platelet counts [2]. The results from the Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) study demonstrated that controlling the hematocrit (HCT) level below 45% was associated with a fourfold reduction in the rates of major thrombotic events and cardiovascular deaths [8]. Hydroxyurea (HU) and phlebotomy were able to achieve a reduction in the rate of cardiovascular death and major thrombosis by controlling the HCT < 45%. No effect on the symptom burden was seen in patients, even after the long-term conventional aggressive therapy in CYTO-PV study [9]. It is well known that nearly a quarter of patients discontinue the first-line therapy (HU or interferon) due to the development of resistance or intolerance to treatment [10,11,12]

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Conclusion