Publication: Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.
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Date
2020
Authors
Fenaux, Pierre
Platzbecker, Uwe
Mufti, Ghulam J
Garcia-Manero, Guillermo
Buckstein, Rena
Santini, Valeria
Díez-Campelo, María
Finelli, Carlo
Cazzola, Mario
Ilhan, Osman
Advisors
Journal Title
Journal ISSN
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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 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.).
Description
MeSH Terms
Activin Receptors, Type II
Adult
Aged
Aged, 80 and over
Anemia, Sideroblastic
Double-Blind Method
Erythrocyte Transfusion
Female
Hematinics
Hemoglobins
Humans
Immunoglobulin Fc Fragments
Infusions, Subcutaneous
Male
Middle Aged
Myelodysplastic Syndromes
Recombinant Fusion Proteins
Adult
Aged
Aged, 80 and over
Anemia, Sideroblastic
Double-Blind Method
Erythrocyte Transfusion
Female
Hematinics
Hemoglobins
Humans
Immunoglobulin Fc Fragments
Infusions, Subcutaneous
Male
Middle Aged
Myelodysplastic Syndromes
Recombinant Fusion Proteins