Publication:
A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia

Issued Date

2020-03-26

Resource Type

Article

ISSN

15334406
00284793

DOI

10.1056/NEJMoa1910182

Other identifier(s)

2-s2.0-85082380437

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

New England Journal of Medicine. Vol.382, No.13 (2020), 1219-1231

Suggested Citation

M. Domenica Cappellini, Vip Viprakasit, Ali T. Taher, Pencho Georgiev, Kevin H.M. Kuo, Thomas Coates, Ersi Voskaridou, Hong Keng Liew, Idit Pazgal-Kobrowski, G. L. Forni, Silverio Perrotta, Abderrahim Khelif, Ashutosh Lal, Antonis Kattamis, Efthymia Vlachaki, Raffaella Origa, Yesim Aydinok, Mohamed Bejaoui, P. Joy Ho, Lee Ping Chew, Ping Chong Bee, Soo Min Lim, Meng Yao Lu, Adisak Tantiworawit, Penka Ganeva, Liana Gercheva, Farrukh Shah, Ellis J. Neufeld, Alexis Thompson, Abderrahmane Laadem, Jeevan K. Shetty, Jun Zou, Jennie Zhang, Dimana Miteva, Tatiana Zinger, Peter G. Linde, Matthew L. Sherman, Olivier Hermine, John Porter, Antonio Piga A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. New England Journal of Medicine. Vol.382, No.13 (2020), 1219-1231. doi:10.1056/NEJMoa1910182 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/54614

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Title

A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia

Author(s)

M. Domenica Cappellini
 Vip Viprakasit
 Ali T. Taher
 Pencho Georgiev
 Kevin H.M. Kuo
 Thomas Coates
 Ersi Voskaridou
 Hong Keng Liew
 Idit Pazgal-Kobrowski
 G. L. Forni
 Silverio Perrotta
 Abderrahim Khelif
 Ashutosh Lal
 Antonis Kattamis
 Efthymia Vlachaki
 Raffaella Origa
 Yesim Aydinok
 Mohamed Bejaoui
 P. Joy Ho
 Lee Ping Chew
 Ping Chong Bee
 Soo Min Lim
 Meng Yao Lu
 Adisak Tantiworawit
 Penka Ganeva
 Liana Gercheva
 Farrukh Shah
 Ellis J. Neufeld
 Alexis Thompson
 Abderrahmane Laadem
 Jeevan K. Shetty
 Jun Zou
 Jennie Zhang
 Dimana Miteva
 Tatiana Zinger
 Peter G. Linde
 Matthew L. Sherman
 Olivier Hermine
 John Porter
 Antonio Piga

Other Contributor(s)

l'Institut des Maladies Génétiques Imagine
 Azienda Ospedaliera Brotzu - Microcitemico
 Centre National de Greffe de Moelle Osseuse
 University Hospital St. Marina
 American University of Beirut Medical Center
 Hopital Farhat Hached Sousse
 UCSF Benioff Children‘s Hospital
 Università degli Studi di Milano
 National and Kapodistrian University of Athens
 St.George University Hospital
 Hôpital Necker Enfants Malades
 Università degli Studi della Campania Luigi Vanvitelli
 Laikon General Hospital
 UCL
 Rabin Medical Center Israel
 St. Jude Children's Research Hospital
 Celgene Corporation
 E.O. Ospedali Galliera
 Royal Prince Alfred Hospital
 University of Toronto
 Keck School of Medicine of USC
 University of Malaya Medical Centre
 Hospital Sultanah Aminah
 Università degli Studi di Torino
 Faculty of Medicine, Siriraj Hospital, Mahidol University
 Ege University Medical School
 National Health Service
 National Taiwan University
 Hippokration General Hospital
 Chiang Mai University
 Celgene
 Hospital Umum
 Ann and Robert H. Lurie Children's Hospital of Chicago
 Specialized Hospital for Active Treatment in Oncology
 Hospital Sultanah Bahiyah
 Acceleron Pharma

Abstract

© 2020 Massachusetts Medical Society. 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.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/54614

Collections

Scopus 2020