N Engl J Med 2020 01;382(2):140-151
From Service d'Hématologie Séniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris and Université Paris 7, Paris (P.F., L.A.), Service des Maladies du Sang, Hôpital Huriez, Centre Hospitalier Universitaire (CHU) de Lille, Lille (B.Q.), the Department of Internal Medicine, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Toulouse (O.B.-R.), and Université Cote d'Azur, Département d'Hématologie Clinique, CHU Nice, Nice (T.C.) - all in France; Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig (U.P.), Klinik für Hämatologie, Onkologie, and Klinische Immunologie, Universitätsklinik Düsseldorf, Düsseldorf (U.G.), and Klinik und Poliklinik für Innere Medizin III, Technische Universität München, Munich (K.S.G.) - all in Germany; the Department of Haemato-Oncology, King's College London, London (G.J.M.), Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford (P.V.), and the Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds (D.B.) - all in the United Kingdom; the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (G.G.-M.); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (R.B.); MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence (V.S.), the Department of Oncology and Hematology, S. Orsola-Malpighi University Hospital, Bologna (C.F.), the University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia (M.C.), the Hematology Unit, Santi Antonio e Biagio e Cesare Arrigo Hospital, Alessandria (F.S., V.G.), and Dipartimento Biomedicina e Prevenzione, University of Rome Tor Vergata, Rome (M.-T.V.) - all in Italy; the Hematology Department, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca, Salamanca (M.D.-C.), Unidad de Hematología, Hospital Universitario Virgen del Rocío, Seville (J.F.F.), and the Department of Hematology, Hospital Universitario Cruces, Vizcaya (B.A.) - all in Spain; the Department of Hematology Science, School of Medicine, Ankara University, Ankara, Turkey (O.I.); the Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland (M.A.S.); the Department of Hematology, Algemeen Ziekenhuis Sint-Jan, Bruges (D.S.), and Universitair Ziekenhuis Gent, Ghent (D.M.) - both in Belgium; the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (A.E.D.); the Division of Hematology-Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center (J.G.J.), and Albert Einstein College of Medicine (A.V.) - both in New York; the Department of Hematology, University Medical Center of Groningen, University of Groningen, Groningen, the Netherlands (E.V.); Stanford University Cancer Center, Stanford, CA (P.L.G.); the Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Stockholm (E.H.-L.); the Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT (A.M.Z.); Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville (M.R.S.); Celgene, Summit, NJ (A.L., J.Z., A.R., D.R.D.); Celgene International, Boudry, Switzerland (A.B.); Acceleron Pharma, Cambridge, MA (P.G.L., M.L.S.); and Moffitt Cancer Center, Tampa, FL (R.S.K., A.F.L.).
Background: Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study.
Methods: In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1. Read More