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

Abstract

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 × 10(9)/L) and randomized to romiplostim 500 μg or 750 μg 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 μg, romiplostim 750 μg, 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 μg 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.

Trial registration: ClinicalTrials.gov NCT00321711.

Figures

Figure 1

Patient disposition. *Stratified by baseline platelet count ≥ or < 50 × 109/L.

Figure 2

Effect of romiplostim on the incidence of clinically significant thrombocytopenic events (left panel) and platelet transfusions (right panel). CI indicstes confidence interval.

Figure 3

Effect of romiplostim on the median platelet counts over time.

Figure 4

Effect of romiplostim on median platelet counts on day 1 of each treatment cycle (left panel) and on median platelet counts at nadir during each treatment cycle (right panel). P values in a nonparametric test comparing median platelet counts between the romiplostim 500-μg and placebo groups were 0.4233, 0.8389, 0.8389, and 0.8137 on day 1 of cycles 1, 2, 3, and 4, respectively, and 0.4986, 0.2905, 0.2905, and 0.5093 at the nadir of cycles 1, 2, 3, and 4, respectively. P values comparing median platelet counts between the romiplostim 750-μg and placebo groups were 0.8445, 0.2289, 0.0373, and 0.1198 on day 1 of cycles 1, 2, 3, and 4, respectively, and 0.3408, 0.2289, 0.0035, and 0.3833 at the nadir of cycles 1, 2, 3, and 4, respectively.