@article{3104621,
    title = "A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia",
    author = "Domenica Cappellini, M. and Viprakasit, V. and Taher, A.T. and Georgiev, P. and Kuo, K.H.M. and Coates, T. and Voskaridou, E. and Liew, H.-K. and Pazgal-Kobrowski, I. and Forni, G.L. and Perrotta, S. and Khelif, A. and Lal, A. and Kattamis, A. and Vlachaki, E. and Origa, R. and Aydinok, Y. and Bejaoui, M. and Joy Ho, P. and Chew, L.-P. and Bee, P.-C. and Lim, S.-M. and Lu, M.-Y. and Tantiworawit, A. and Ganeva, P. and Gercheva, L. and Shah, F. and Neufeld, E.J. and Thompson, A. and Laadem, A. and Shetty, J.K. and Zou, J. and Zhang, J. and Miteva, D. and Zinger, T. and Linde, P.G. and Sherman, M.L. and Hermine, O. and Porter, J. and Piga, A. and BELIEVE Investigators",
    journal = "The New England journal of medicine",
    year = "2020",
    volume = "382",
    number = "13",
    pages = "1219-1231",
    publisher = "Massachussetts Medical Society",
    doi = "10.1056/NEJMoa1910182",
    keywords = "luspatercept;  placebo;  activin receptor 2;  antianemic agent;  ferritin;  fusion protein;  immunoglobulin Fc fragment;  luspatercept, adult;  adverse outcome;  aged;  arthralgia;  Article;  beta thalassemia;  bone pain;  controlled study;  dizziness;  double blind procedure;  drug efficacy;  drug safety;  female;  human;  hypertension;  hyperuricemia;  major clinical study;  male;  outcome assessment;  phase 3 clinical trial;  priority journal;  randomized controlled trial;  adolescent;  beta thalassemia;  blood;  clinical trial;  erythrocyte transfusion;  genetics;  intention to treat analysis;  least square analysis;  middle aged;  multicenter study;  odds ratio;  splenectomy;  young adult, Activin Receptors, Type II;  Adolescent;  Adult;  Aged;  beta-Thalassemia;  Double-Blind Method;  Erythrocyte Transfusion;  Female;  Ferritins;  Hematinics;  Humans;  Immunoglobulin Fc Fragments;  Intention to Treat Analysis;  Least-Squares Analysis;  Male;  Middle Aged;  Odds Ratio;  Recombinant Fusion Proteins;  Splenectomy;  Young Adult",
    abstract = "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 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was −348 μg per liter (95% confidence interval, −517 to −179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. © 2020 Massachusetts Medical Society."
}