%0 Journal Article
%A Fenaux, Pierre
%A Platzbecker, Uwe
%A Mufti, Ghulam J
%A Garcia-Manero, Guillermo
%A Buckstein, Rena
%A Santini, Valeria
%A Díez-Campelo, María
%A Finelli, Carlo
%A Cazzola, Mario
%A Ilhan, Osman
%A Sekeres, Mikkael A
%A Falantes, José F
%A Arrizabalaga, Beatriz
%A Salvi, Flavia
%A Giai, Valentina
%A Vyas, Paresh
%A Bowen, David
%A Selleslag, Dominik
%A DeZern, Amy E
%A Jurcic, Joseph G
%A Germing, Ulrich
%A Götze, Katharina S
%A Quesnel, Bruno
%A Beyne-Rauzy, Odile
%A Cluzeau, Thomas
%A Voso, Maria-Teresa
%A Mazure, Dominiek
%A Vellenga, Edo
%A Greenberg, Peter L
%A Hellström-Lindberg, Eva
%A Zeidan, Amer M
%A Adès, Lionel
%A Verma, Amit
%A Savona, Michael R
%A Laadem, Abderrahmane
%A Benzohra, Aziz
%A Zhang, Jennie
%A Rampersad, Anita
%A Dunshee, Diana R
%A Linde, Peter G
%A Sherman, Matthew L
%A Komrokji, Rami S
%A List, Alan F
%T Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.
%D 2020
%U http://hdl.handle.net/10668/14931
%X Patients 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.).
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