A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy

Summary Givinostat, a histone‐deacetylase inhibitor ( HDAC i), inhibits proliferation of cells bearing the JAK 2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms ( MPN ). In this multicentre, open‐label, phase II study, 44 patients with polycythaemia vera ( PV ), unresponsive to the maximum tolerated doses ( MTD ) of hydroxycarbamide ( HC ), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC . The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC ‐unresponsive PV patients.