Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes

Fenaux, P., Platzbecker, U., Mufti, G. J., Garcia-Manero, G., Buckstein, R., Santini, V., Diez-Campelo, M., Finelli, C., Cazzola, M., Ilhan, O., Sekeres, M. A., Falantes, J. F., Arrizabalaga, B., Salvi, F., Giai, V., Vyas, P., Bowen, D., Selleslag, D., DeZern, A. E., Jurcic, J. G., Germing, U., Goetze, K. S., Quesnel, B., Beyne-Rauzy, O., Cluzeau, T., Voso, M-T., Mazure, D., Vellenga, E., Greenberg, P. L., Hellstrom-Lindberg, E., Zeidan, A. M., Ades, L., Verma, A., Savona, M. R., Laadem, A., Benzohra, A., Zhang, J., Rampersad, A., Dunshee, D. R., Linde, P. G., Sherman, M. L., Komrokji, R. S. & List, A. F., 9-Jan-2020, In : New England Journal of Medicine. 382, 2, p. 140-151 12 p.

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  • Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes

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  • Pierre Fenaux
  • Uwe Platzbecker
  • Ghulam J. Mufti
  • Guillermo Garcia-Manero
  • Rena Buckstein
  • Valeria Santini
  • Maria Diez-Campelo
  • Carlo Finelli
  • Mario Cazzola
  • Osman Ilhan
  • Mikkael A. Sekeres
  • Jose F. Falantes
  • Beatriz Arrizabalaga
  • Flavia Salvi
  • Valentina Giai
  • Paresh Vyas
  • David Bowen
  • Dominik Selleslag
  • Amy E. DeZern
  • Joseph G. Jurcic
  • Ulrich Germing
  • Katharina S. Goetze
  • Bruno Quesnel
  • Odile Beyne-Rauzy
  • Thomas Cluzeau
  • Maria-Teresa Voso
  • Dominiek Mazure
  • Edo Vellenga
  • Peter L. Greenberg
  • Eva Hellstrom-Lindberg
  • Amer M. Zeidan
  • Lionel Ades
  • Amit Verma
  • Michael R. Savona
  • Abderrahmane Laadem
  • Aziz Benzohra
  • Jennie Zhang
  • Anita Rampersad
  • Diana R. Dunshee
  • Peter G. Linde
  • Matthew L. Sherman
  • Rami S. Komrokji
  • Alan F. List

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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 number, NCT02631070; EudraCT number, 2015-003454-41.).

Original languageEnglish
Pages (from-to)140-151
Number of pages12
JournalNew England Journal of Medicine
Issue number2
Publication statusPublished - 9-Jan-2020



ID: 111972970