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Clinical Trial
. 2018 Dec;32(12):2648-2658.
doi: 10.1038/s41375-018-0118-9. Epub 2018 Mar 30.

A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS

Pierre Fenaux  1 , Valeria Santini  2 , Maria Antonietta Aloe Spiriti  3 , Aristoteles Giagounidis  4 , Rudolf Schlag  5 , Atanas Radinoff  6 , Liana Gercheva-Kyuchukova  7 , Achilles Anagnostopoulos  8 , Esther Natalie Oliva  9 , Argiris Symeonidis  10 , Mathilde Hunault Berger  11 , Katharina S Götze  12 , Anna Potamianou  13 , Hari Haralampiev  14 , Robert Wapenaar  15 , Iordanis Milionis  16 , Uwe Platzbecker  17
Affiliations
Clinical Trial

A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS

Pierre Fenaux et al. Leukemia. 2018 Dec.

Abstract

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.

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Conflict of interest statement

Received research funding from Janssen-Cilag: AA, ENO, LG-K. Received research funding and honoraria from Janssen-Cilag: AS, KSG. Received honoraria from Janssen-Cilag: MHB, UP, and VS. Employees of Janssen: AP, HH, IM, RW. Johnson & Johnson stockholder: AP. The remaining authors declare no conflict of interest: AG, AR, MAAS, PF, and RS.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram
Fig. 2
Fig. 2
Time-to-first-red blood cell (RBC)-transfusions (mITT)
Fig. 3
Fig. 3
Time-to-first-red blood cell (RBC)-transfusions after week 4 by RRC responder status (mITT)
See this image and copyright information in PMC

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