Safety and Efficacy of Romiplostim in Patients With Lower-Risk Myelodysplastic Syndrome and Thrombocytopenia

Radboud University Nijmegen, Nymegen, Gelderland, Netherlands
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2009; 28(3):437-44. DOI: 10.1200/JCO.2009.24.7999
Source: PubMed


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.

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    • "While the majority of combination studies using DMNTIs were conducted in the higher-risk MDS population, the combination of romiplostin with azacitidine or decitabine has proven to be safe and effective in the lower-risk population, resulting in higher median platelet counts and fewer CSTE when compared to patients receiving DNMTIs alone [31] [74]. Gemtuzumab ozogamicin (GO) is an anti-CD33 monoclonal antibody that is bound to the cytototxic agent calicheamicin and has demonstrated significant activity in AML [75] [76] A phase II trial combined GO and the apoptotic and pro-differentiating agent arsenic trioxide (ATO) in patients with CD33 þ secondary AML (sAML) and MDS. "
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    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.
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    • "There is some evidence for the use of danazol in selected patients, in terms of short-term improvement in the platelet count (Wattel et al, 1994; Chan et al, 2002). The thrombopoietin receptor (Tpo-R) agonist, romiplostim has been evaluated in a large randomized phase 2 study following an encouraging dose finding study (Kantarjian et al, 2010). The study was halted prematurely because of concerns about increasing blast cell counts in patients receiving active drug. "
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    • "Romiplostim is indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy [18]. It has been investigated for treatment of MDS patients with or without del (5q) [19-23]. In phase 1/2 studies, 46–65% of lower-risk thrombocytopenic MDS patients receiving romiplostim achieved an International Working Group (IWG)-defined platelet response [19,20,24]. "
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