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 g or 750 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 g, romiplostim 750 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 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%

Safety and feasibility of romiplostim treatment for patients with persistent thrombocytopenia after allogeneic stem cell transplantation

“…10,11 The occurrence of SFPR concomitantly with GvHD and/or infectious complications, together with the toxicity of the treatment, especially in the setting of haploidentical HSCT are in line with previous reports. 6 Romiplostim treatment is effective especially in patients with SFPR, reducing transfusion needs and hemorrhagic risk.…”

Evaluation of noncytotoxic DNMT1-depleting therapy in patients with myelodysplastic syndromes

“…These pathologies emphasize the need for a good therapeutic index in treatments used to suppress myeloid cancer clones (8)(9)(10)(11)(12). Additional treatments that boost functional hematopoiesis and that are FDA approved to treat BM failure, e.g., thrombopoietin receptor (MPL) agonists, can potentially complement clone-suppressing treatments (69,70).…”

Epigenetic Modifications: Therapeutic Potential in Cancer

“…Relevant chemotherapeutic drugs have also been tested in combination with DNMT, HDAC and SIRT inhibitors. A Phase 2 study combined the thrombopoietin mimetic romiplostim with 5-azacytidine in the patients with myelodysplastic syndrome (Kantarjian et al 2010). The combined treatment such as the treatment with panobinostat with sorafenib demonstrated the highest preclinical efficacy in hepatocellular carcinoma models, providing the rationale for the clinical studies with this novel combination (Lachenmayer et al 2012).…”