Ovid: Welcome to Ovid

Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.
Fenaux, Pierre M.D., Ph.D.; Platzbecker, Uwe M.D.; Mufti, Ghulam J. F.R.C.P.; Garcia-Manero, Guillermo M.D.; Buckstein, Rena M.D.; Santini, Valeria M.D.; Diez-Campelo, Maria M.D., Ph.D.; Finelli, Carlo M.D.; Cazzola, Mario M.D.; Ilhan, Osman M.D.; Sekeres, Mikkael A. M.D.; Falantes, Jose F. M.D.; Arrizabalaga, Beatriz M.D.; Salvi, Flavia M.D.; Giai, Valentina M.D., Ph.D.; Vyas, Paresh B.Ch., B.M.; Bowen, David M.D.; Selleslag, Dominik M.D.; DeZern, Amy E. M.D.; Jurcic, Joseph G. M.D.; Germing, Ulrich M.D.; Gotze, Katharina S. M.D.; Quesnel, Bruno M.D., Ph.D.; Beyne-Rauzy, Odile M.D.; Cluzeau, Thomas M.D.; Voso, Maria-Teresa M.D.; Mazure, Dominiek M.D.; Vellenga, Edo M.D., Ph.D.; Greenberg, Peter L. M.D.; Hellstrom-Lindberg, Eva M.D.; Zeidan, Amer M. M.B., B.S., M.H.S.; Ades, Lionel M.D.; Verma, Amit M.D.; Savona, Michael R. M.D.; Laadem, Abderrahmane M.D.; Benzohra, Aziz M.D.; Zhang, Jennie M.S.; Rampersad, Anita B.A.; Dunshee, Diana R. Ph.D.; Linde, Peter G. M.D.; Sherman, Matthew L. M.D.; Komrokji, Rami S. M.D.; List, Alan F. M.D.
[Article] New England Journal of Medicine. 382(2):140-151, January 9, 2020.

(Format: HTML, PDF)

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 [beta] 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.)