Safety and Efficacy of Romiplostim in Patients With Lower-Risk Myelodysplastic Syndrome and Thrombocytopenia
ABSTRACT To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS).
Eligible patients had lower-risk MDS (International Prognostic Scoring System low or intermediate 1), a mean baseline platelet count <or= 50 x 10(9)/L, and were only receiving supportive care. Patients received three injections of 300, 700, 1,000, or 1,500 microg romiplostim at weekly intervals. After evaluation of platelet response at week 4, patients could continue to receive romiplostim in a treatment extension phase for up to 1 year.
All 44 patients who enrolled completed the treatment phase; 41 patients continued into the extension phase. Median platelet counts increased throughout the study, from fewer than 30 x 10(9)/L at baseline to 60, 73, 38, and 58 x 10(9)/L at week 4 for the 300-, 700-, 1,000-, and 1,500 -microg dose cohorts, respectively. A durable platelet response (per International Working Group 2000 criteria for 8 consecutive weeks independent of platelet transfusions) was achieved by 19 patients (46%). The incidence of bleeding events and platelet transfusions was less common among patients who achieved a durable platelet response than those who did not (4.3 v 39.3 per 100 patient-weeks). Forty-three patients (98%) reported one or more adverse events. Treatment-related serious adverse events were reported in five patients (11%), all of whom were in the 1,500-microg dose cohort. Two patients progressed to acute myeloid leukemia during the study. No neutralizing antibodies to either romiplostim or endogenous thrombopoietin were seen.
Romiplostim appeared well-tolerated in this study and may be a useful treatment for patients with MDS and thrombocytopenia.
SourceAvailable from: Sudipto Mukherjee[Show abstract] [Hide abstract]
ABSTRACT: The myelodysplastic syndromes (MDS) are a heterogenous collection of clonal hematopoietic malignancies that exist as a subgroup of the myeloid neoplasms as classified by the World Health Organization (WHO). They are characterized by ineffective hematopoiesis, subsequent cytopenias, transformation to acute myeloid leukemia (AML), and poor overall survival. There are currently three FDA-approved medications for MDS; lenalidomide, azacitidine, and decitabine. The role of these agents is to diminish the clinical impact of MDS and delay its progression to AML. However, despite known results with these monotherapies, recent clinical trials with a variety of combinations for MDS have demonstrated promising results. These trials include combinations of hypomethylating agents, histone deacetylase inhibitors, growth factors, and chemotherapy among others. In this paper we review the current literature on combination therapies in MDS, analyze on-going and concluded trials, and suggest future possibilities for combination strategies in MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.Bailliè re s Best Practice and Research in Clinical Haematology 11/2014; 28(1). DOI:10.1016/j.beha.2014.11.002 · 2.55 Impact Factor
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ABSTRACT: Thrombopoietic agents have created a paradigm shift in the management of chronic or poorly responsive ITP. There are ample randomized, placebo-controlled trial data as well as long term data gathered for more than 5 years: short term efficacy and safety are well documented and long-term efficacy and safety data are emerging. The purpose of this review will be to focus critically on what we know or do not know at this point about these agents. We will review evolution, efficacy and clinical use, side effects, special populations, and off target effects.Seminars in Hematology 11/2014; 52(1). DOI:10.1053/j.seminhematol.2014.11.001 · 2.46 Impact Factor
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ABSTRACT: Myelodysplastic syndromes are clinically, genetically and molecularly heterogeneous neoplastic diseases characterized by ineffective hematopoiesis leading to peripheral cytopenias. The severity of cytopenias influences oucome and is considered in prognostic scoring systems; thrombocytopenia, although not the most frequently observed at disease onset, is estimated to affect 40-80% of MDS patients. As thrombocytopenia in MDS is determined by premature marrow destruction and programmed cell death, the use of thrombomimetic agents has been proposed in order to stimulate megakaryocyte differentation and proliferation. After early attempts of therapy of thrombocytopenic MDS patients with thrombopoietin and IL-11, clinical trials testing the activity of romiplostim and eltrombopag have been recently designed and have demonstrated good tolerability and efficacy in re-inducing megakaryocytopoiesis and in lowering the number of hemorragic events. The number of MDS patients receiving such treatments is still limited and a broader evaluation of the long term effects and safety of these agents is ongoing.Seminars in Hematology 10/2014; DOI:10.1053/j.seminhematol.2014.10.005 · 2.46 Impact Factor