Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. The New England journal of medicine Fenaux, P. n., Platzbecker, U. n., Mufti, G. J., Garcia-Manero, G. n., Buckstein, R. n., Santini, V. n., Díez-Campelo, M. n., Finelli, C. n., Cazzola, M. n., Ilhan, O. n., Sekeres, M. A., Falantes, J. F., Arrizabalaga, B. n., Salvi, F. n., Giai, V. n., Vyas, P. n., Bowen, D. n., Selleslag, D. n., DeZern, A. E., Jurcic, J. G., Germing, U. n., Götze, K. S., Quesnel, B. n., Beyne-Rauzy, O. n., Cluzeau, T. n., Voso, M. T., Mazure, D. n., Vellenga, E. n., Greenberg, P. L., Hellström-Lindberg, E. n., Zeidan, A. M., Adès, L. n., Verma, A. n., Savona, M. R., Laadem, A. n., Benzohra, A. n., Zhang, J. n., Rampersad, A. n., Dunshee, D. R., Linde, P. G., Sherman, M. L., Komrokji, R. S., List, A. F. 2020; 382 (2): 140–51

Abstract

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 ß 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<0.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point (28% vs. 8% for weeks 1 through 24, and 33% vs. 12% for weeks 1 through 48; P<0.001 for both comparisons). The most common luspatercept-associated adverse events (of any grade) included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time.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.).

View details for DOI 10.1056/NEJMoa1908892

View details for PubMedID 31914241