Fenaux, PierrePlatzbecker, UweMufti, Ghulam JGarcia-Manero, GuillermoBuckstein, RenaSantini, ValeriaDíez-Campelo, MaríaFinelli, CarloCazzola, MarioIlhan, OsmanSekeres, Mikkael AFalantes, José FArrizabalaga, BeatrizSalvi, FlaviaGiai, ValentinaVyas, PareshBowen, DavidSelleslag, DominikDeZern, Amy EJurcic, Joseph GGerming, UlrichGötze, Katharina SQuesnel, BrunoBeyne-Rauzy, OdileCluzeau, ThomasVoso, Maria-TeresaMazure, DominiekVellenga, EdoGreenberg, Peter LHellström-Lindberg, EvaZeidan, Amer MAdès, LionelVerma, AmitSavona, Michael RLaadem, AbderrahmaneBenzohra, AzizZhang, JennieRampersad, AnitaDunshee, Diana RLinde, Peter GSherman, Matthew LKomrokji, Rami SList, Alan F2023-02-082023-02-082020http://hdl.handle.net/10668/14931Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study. In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.0 up to 1.75 mg per kilogram of body weight) or placebo, administered subcutaneously every 3 weeks. The primary end point was transfusion independence for 8 weeks or longer during weeks 1 through 24, and the key secondary end point was transfusion independence for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. Of the 229 patients enrolled, 153 were randomly assigned to receive luspatercept and 76 to receive placebo; the baseline characteristics of the patients were balanced. Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event. (Funded by Celgene and Acceleron Pharma; MEDALIST ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.).enActivin Receptors, Type IIAdultAgedAged, 80 and overAnemia, SideroblasticDouble-Blind MethodErythrocyte TransfusionFemaleHematinicsHemoglobinsHumansImmunoglobulin Fc FragmentsInfusions, SubcutaneousMaleMiddle AgedMyelodysplastic SyndromesRecombinant Fusion Proteinsresearch article31914241open access10.1056/NEJMoa19088921533-4406https://doi.org/10.1056/nejmoa1908892