Romiplostim monotherapy in thrombocytopenic patients with myelodysplastic syndromes: long-term safety and efficacy

Pierre Fenaux, Petra Muus, Hagop Kantarjian, Roger M Lyons, Richard A Larson, Mikkael A Sekeres, Pamela S Becker, Amelia Orejudos, Janet Franklin, Pierre Fenaux, Petra Muus, Hagop Kantarjian, Roger M Lyons, Richard A Larson, Mikkael A Sekeres, Pamela S Becker, Amelia Orejudos, Janet Franklin

Abstract

Romiplostim can improve platelet counts in about 50% of patients with low- or intermediate 1-risk (lower risk) myelodysplastic syndromes (MDS) and thrombocytopenia, but its long-term toxicity and efficacy are not known. This open-label extension study evaluated the long-term safety and efficacy of romiplostim in 60 patients with lower risk MDS and platelet counts ≤50 × 109 /l. The primary endpoint was adverse event (AE) incidence. Secondary endpoints were efficacy parameters, including bleeding events and platelet response. Median (range) treatment time in the extension study and the median observation times thereafter were 25 (2-181) and 57 (11-209) weeks, respectively. Treatment-related AEs and serious AEs were reported in 14/60 (23%) and 4/60 (7%) patients, respectively. Progression to acute myeloid leukaemia (AML) occurred in two patients after 44 and 46 weeks. Patients (n = 34, 57%) with a platelet response were further evaluated for length of response. Median (range) response duration was 33 (7-174) weeks; 28/34 (82%) patients had a continuous response. Five of 34 patients (15%) had grade ≥3 bleeding events; three when the platelet count was >50 × 109 /l. There were no new safety concerns and the rate of progression to AML was low; response to romiplostim was maintained for most patients.

Trial registration: ClinicalTrials.gov NCT00472290.

Keywords: myelodysplastic syndromes; platelets; romiplostim; thrombocytopenia; thrombopoietin receptor agonist.

© 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Study design and treatment schema. Patients were enrolled from one of two parent studies: (i) a 52‐week, phase 1/2 study of once‐weekly romiplostim 300–1500 μg (Kantarjian et al, 2010; Sekeres et al, 2011); (ii) a 58‐week, randomised, phase 2, placebo‐controlled study of once‐weekly romiplostim 750 μg.(Giagounidis et al, 2014) *Response per IWG 2006 criteria (Cheson et al, 2006) (Table 2). AML, acute myeloid leukaemia.
Figure 2
Figure 2
(A) Median platelet counts over time and (B) incidence of bleeding events among patients with platelet response in the open‐label extension exposed to romiplostim during the time interval. Q1, Q3 = interquartile range.

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