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

• DOI: 10.1038/s41375-018-0118-9
• Publication Date: 2018-04-04T02:01:17Z
• Authors: Pierre Fenaux; Valeria Santini; Maria Antonietta ...; Aristoteles Giago...; Rudolf Schlag; Atanas Radinoff; Liana Gercheva-Ky...; Achilles Anagnost...; Esther Natalie Oliva; Argiris Symeonidis; Mathilde Hunault ...; Katharina S. Götze; Anna Potamianou; Hari Haralampiev; Robert Wapenaar; Iordanis Milionis; Uwe Platzbecker
• Keywords: Discontinuation; Epoetin alfa; Clinical endpoint

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