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<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 luspaterceptassociated
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 erythropoiesisstimulating
agents or who had discontinued such agents owing to an adverse event.
Venetoclax (Venclyxto*, Abbvie) bénéficie d’une ATU de cohorte dans les leucémies aigües myéloïdes