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A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia.

N Engl J Med

March 2020

From the Department of Clinical Sciences and Community, University of Milan, IRCCS Ca' Granda Foundation Maggiore Policlinico Hospital, Milan (M.D.C.), Centro della Microcitemia e Anemie Congenite e del Dismetabolismo del Ferro, E.O. Ospedali Galliera, Genoa (G.L.F.), Ospedale Pediatrico Microcitemico A. Cao, Azienda Ospedaliera G. Brotzu, Cagliari (R.O.), Ematologia e Oncologia Pediatrica, Università della Campania L. Vanvitelli, Caserta (S.P.), and the Department of Clinical and Biological Sciences, University of Turin, Turin (A.P.) - all in Italy; Siriraj Hospital, Mahidol University, Bangkok (V.V.), and the Division of Hematology, Department of Internal Medicine, Chiang Mai University, Chiang Mai (A. Tantiworawit) - both in Thailand; the Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon (A.T.T.); St. George University Hospital for Active Treatment and Medical University of Plovdiv, Plovdiv (P. Georgiev), University Specialized Hospital for Active Treatment in Oncology, Sofia (P. Ganeva), and University Hospital St. Marina, Varna (L.G.) - all in Bulgaria; the Division of Medical Oncology and Hematology, Department of Medicine, University Health Network and Division of Hematology, Department of Medicine, University of Toronto, Toronto (K.H.M.K.); the Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, and Keck School of Medicine of the University of Southern California, Los Angeles (T.C.), and the University of California San Francisco Benioff Children's Hospital, Oakland (A. Lal) - all in California; the Thalassemia and Sickle Cell Center, Laiko General Hospital (E. Voskaridou), and the First Department of Pediatrics, National and Kapodistrian University of Athens (A. Kattamis), Athens, and the Adult Thalassemia Unit, Hippokration Hospital, Thessaloniki (E. Vlachaki) - all in Greece; Hospital Sultanah Bahiyah, Alor Setar (H.K.L.), Hospital Umum, Sarawak, Kuching (L.P.C.), the University of Malaya Medical Center, Kuala Lumpur (P.C.B.), and Hospital Sultanah Aminah, Johor Bahru (S.M.L.) - all in Malaysia; the Comprehensive Center of Thalassemia, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel (I.P.-K.); Farhat Hached University Hospital, Sousse (A. Khelif), and the National Bone Marrow Transplant Center and Faculty of Medicine, University of Tunis El Manar, Tunis (M.B.) - both in Tunisia; the Department of Pediatric Hematology and Oncology, Ege University Hospital, Izmir, Turkey (Y.A.); Royal Prince Alfred Hospital and the University of Sydney, Sydney (P.J.H.); National Taiwan University, Taipei, Taiwan (M.-Y. L.); the Department of Haematology, Whittington Health NHS Trust (F.S.), and the Department of Haematology, University College London and University College London Hospitals NHS Foundation Trust (J.P.) - all in London; St. Jude Children's Research Hospital, Memphis, TN (E.J.N.); Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago (A. Thompson); Celgene, Summit, NJ (A. Laadem, J. Zou, J. Zhang); Celgene, Boudry, Switzerland (J.K.S., D.M., T.Z.); Acceleron Pharma, Cambridge, MA (P.G.L., M.L.S.); and the Department of Hematology, Necker Hospital, Assistance Publique-Hôpitaux de Paris (O.H.), and Imagine Institute, INSERM Unité 1163, University of Paris (O.H.) - both in Paris.

Background: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.

Methods: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.

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