TY - JOUR
T1 - A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia
AU - BELIEVE Investigators
AU - Domenica Cappellini, M.
AU - Viprakasit, Vip
AU - Taher, Ali T.
AU - Georgiev, Pencho
AU - Kuo, Kevin H.M.
AU - Coates, Thomas
AU - Voskaridou, Ersi
AU - Liew, Hong Keng
AU - Pazgal-Kobrowski, Idit
AU - Forni, G. L.
AU - Perrotta, Silverio
AU - Khelif, Abderrahim
AU - Lal, Ashutosh
AU - Kattamis, Antonis
AU - Vlachaki, Efthymia
AU - Origa, Raffaella
AU - Aydinok, Yesim
AU - Bejaoui, Mohamed
AU - Joy Ho, P.
AU - Chew, Lee Ping
AU - Bee, Ping Chong
AU - Lim, Soo Min
AU - Lu, Meng Yao
AU - Tantiworawit, Adisak
AU - Ganeva, Penka
AU - Gercheva, Liana
AU - Shah, Farrukh
AU - Neufeld, Ellis J.
AU - Thompson, Alexis
AU - Laadem, Abderrahmane
AU - Shetty, Jeevan K.
AU - Zou, Jun
AU - Zhang, Jennie
AU - Miteva, Dimana
AU - Zinger, Tatiana
AU - Linde, Peter G.
AU - Sherman, Matthew L.
AU - Hermine, Olivier
AU - Porter, John
AU - Piga, Antonio
N1 - Publisher Copyright:
© 2020 Massachusetts Medical Society.
PY - 2020/3/26
Y1 - 2020/3/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85082380437&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1910182
DO - 10.1056/NEJMoa1910182
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C2 - 32212518
AN - SCOPUS:85082380437
SN - 0028-4793
VL - 382
SP - 1219
EP - 1231
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 13
ER -