Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy

We evaluated the efficacy and safety of romiplostim, a thrombopoietin mimetic, in patients with low-or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine therapy. Forty patients with low-or intermediate-risk MDS were stratified by baseline platelet counts (< 50 vs >= 50 x 10(9)/L) and randomized to romiplostim 500 mu g or 750 mu g or placebo subcutaneously once weekly during 4 cycles of azacitidine. The primary endpoint was the incidence of clinically significant thrombocytopenic events, defined by grade 3 or 4 thrombocytopenia starting on day 15 of the first cycle or platelet transfusion at any time during the 4-cycle treatment period. No formal hypothesis testing was planned. The incidence of clinically significant thrombocytopenic events in patients receiving romiplostim 500 mu g, romiplostim 750 mu g, or placebo was 62%, 71%, and 85%, respectively. The incidence of platelet transfusions was 46%, 36%, and 69%, respectively. These differences were not statistically significant with the small numbers in each group. Romiplostim 750 mu g significantly raised median platelet counts during cycle 3 on day 1 (P = .0373) and at the nadir (P = .0035) compared with placebo. Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient (4%). This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy. This study was registered at www.clinicaltrials.gov as #NCT00321711. (Blood. 2010; 116(17): 3163-3170)