TY - JOUR
TI - A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia
AU - Domenica Cappellini, M.
AU - Viprakasit, V.
AU - Taher, A.T.
AU - Georgiev, P.
AU - Kuo, K.H.M.
AU - Coates, T.
AU - Voskaridou, E.
AU - Liew, H.-K.
AU - Pazgal-Kobrowski, I.
AU - Forni, G.L.
AU - Perrotta, S.
AU - Khelif, A.
AU - Lal, A.
AU - Kattamis, A.
AU - Vlachaki, E.
AU - Origa, R.
AU - Aydinok, Y.
AU - Bejaoui, M.
AU - Joy Ho, P.
AU - Chew, L.-P.
AU - Bee, P.-C.
AU - Lim, S.-M.
AU - Lu, M.-Y.
AU - Tantiworawit, A.
AU - Ganeva, P.
AU - Gercheva, L.
AU - Shah, F.
AU - Neufeld, E.J.
AU - Thompson, A.
AU - Laadem, A.
AU - Shetty, J.K.
AU - Zou, J.
AU - Zhang, J.
AU - Miteva, D.
AU - Zinger, T.
AU - Linde, P.G.
AU - Sherman, M.L.
AU - Hermine, O.
AU - Porter, J.
AU - Piga, A.
AU - BELIEVE Investigators
JO - The New England journal of medicine
PY - 2020
VL - 382
TODO - 13
SP - 1219-1231
PB - Massachussetts Medical Society
SN - null
TODO - 10.1056/NEJMoa1910182
TODO - 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
TODO - 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.
ER -