Luspatercept in Patients with Lower-Risk Myelodysplastic SyndromesFenaux, 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.
Research output: Contribution to journal › Article › Academic › peer-review
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 ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.).
|Number of pages||12|
|Journal||New England Journal of Medicine|
|Publication status||Published - 9-Jan-2020|
- INTERNATIONAL WORKING GROUP, PROGNOSTIC SCORING SYSTEM, WORLD-HEALTH-ORGANIZATION, PREDICTING SURVIVAL, LEUKEMIC EVOLUTION, MYELOID NEOPLASMS, RESPONSE CRITERIA, 5Q DELETION, ERYTHROPOIESIS, ANEMIA