Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with lower risk myelodysplastic syndromes

Abstract

BACKGROUND: Romiplostim is a peptibody protein that augments thrombopoiesis by activating the thrombopoietin receptor. METHODS: In this phase 2, multicenter, open-label study, 28 thrombocytopenic patients with lower risk myelodysplastic syndromes (MDS) were assigned to receive romiplostim 750 lg administered subcutaneously either weekly or biweekly or administered as biweekly intravenous injections for 8 weeks. Patients also could enter a 1-year study extension phase. RESULTS: At least 1 adverse event was observed in 93% of patients. The most common adverse events were fatigue and headache (18% for both, and 5 events were grade 3 or 4. There was 1 serious treatment-related adverse event in the biweekly intravenous cohort (hypersensitivity). This hypersensitivity resolved without discontinuation of study treatment. No patients developed neutralizing antibodies or bone marrow fibrosis. Of the patients who completed 8 weeks of treatment, 57% had a complete platelet response, an additional 8% had a major platelet response, and 61% did not require a platelet transfusion during this period. Weekly subcutaneous injections achieved the highest mean trough concentrations. CONCLUSIONS: The safety and efficacy profiles of romiplostim in this study suggested that weekly subcutaneous administration of 750 lg romiplostim is an appropriate starting dose for future clinical studies in patients with MDS and thrombocytopenia. Cancer 2011;117:992

Recent developments in myelodysplastic syndromes

“…31,32 There is increasing off-label use of the thrombopoietin agonists romiplostim and eltrombopag in MDS, despite the potential risk of these agents to augment myeloblast proliferation. 33 Recent data from a placebo-controlled trial of romiplostim in lower-risk MDS are somewhat reassuring, as the rate of progression to AML was not increased with romiplostim therapy, whereas platelet transfusion needs and clinically significant bleeding events were reduced with active therapy. 34 In the alloimmunized patient with severe thrombocytopenia in whom platelet transfusion is difficult, some investigators feel that a numeric increase in blasts may be an acceptable price for transfusion independence and decreased risk of bleeding.…”

Pathogenesis and management of inherited thrombocytopenias: rationale for the use of thrombopoietin-receptor agonists

“…However, in all the IT forms, a careful evaluation of the balance between benefits and risk of thrombosis in individual patients is strongly recommended before TPO-RAs administration. In two clinical trials of romiplostim in myelodysplastic syndromes, some patients experienced increases in peripheral blood blasts and increased risk of transformation to acute leukemia was suggested [101,102]. FPD-AML and ANKR26-RT predispose to myeloid malignancies.…”

How to manage lower-risk myelodysplastic syndromes

“…44 Of 44 patients enrolled into 1 of 4 dose cohorts to receive weekly injections of 300, 700, 1000 or 1500 mg romiplostim, 41 continued into the extension phase of the study with continued weekly injections, and 19 (46%) achieved durable platelet responses. 45 Caution must be used in treating MDS patients with romiplostim, however, as two subjects progressed to AML during the study, and four others had transient increases in blast percentage. A randomized phase II study has just completed enrollment.…”