M. Domenica CappelliniVip ViprakasitAli T. TaherPencho GeorgievKevin H.M. KuoThomas CoatesErsi VoskaridouHong Keng LiewIdit Pazgal-KobrowskiG. L. ForniSilverio PerrottaAbderrahim KhelifAshutosh LalAntonis KattamisEfthymia VlachakiRaffaella OrigaYesim AydinokMohamed BejaouiP. Joy HoLee Ping ChewPing Chong BeeSoo Min LimMeng Yao LuAdisak TantiworawitPenka GanevaLiana GerchevaFarrukh ShahEllis J. NeufeldAlexis ThompsonAbderrahmane LaademJeevan K. ShettyJun ZouJennie ZhangDimana MitevaTatiana ZingerPeter G. LindeMatthew L. ShermanOlivier HermineJohn PorterAntonio Pigal'Institut des Maladies Génétiques ImagineAzienda Ospedaliera Brotzu - MicrocitemicoCentre National de Greffe de Moelle OsseuseUniversity Hospital St. MarinaAmerican University of Beirut Medical CenterHopital Farhat Hached SousseUCSF Benioff Children‘s HospitalUniversità degli Studi di MilanoNational and Kapodistrian University of AthensSt.George University HospitalHôpital Necker Enfants MaladesUniversità degli Studi della Campania Luigi VanvitelliLaikon General HospitalUCLRabin Medical Center IsraelSt. Jude Children's Research HospitalCelgene CorporationE.O. Ospedali GallieraRoyal Prince Alfred HospitalUniversity of TorontoKeck School of Medicine of USCUniversity of Malaya Medical CentreHospital Sultanah AminahUniversità degli Studi di TorinoFaculty of Medicine, Siriraj Hospital, Mahidol UniversityEge University Medical SchoolNational Health ServiceNational Taiwan UniversityHippokration General HospitalChiang Mai UniversityCelgeneHospital UmumAnn and Robert H. Lurie Children's Hospital of ChicagoSpecialized Hospital for Active Treatment in OncologyHospital Sultanah BahiyahAcceleron Pharma2020-05-052020-05-052020-03-26New England Journal of Medicine. Vol.382, No.13 (2020), 1219-123115334406002847932-s2.0-85082380437https://repository.li.mahidol.ac.th/handle/20.500.14594/54614© 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.Mahidol UniversityMedicineArticleSCOPUS10.1056/NEJMoa1910182