Luspatercept Reduces Anemia Severity in Patients With MDS Receiving Transfusions

Among patients with lower-risk myelodysplastic syndromes (MDS) receiving regular red-cell transfusions in a phase 3 trial, treatment with luspatercept reduced the severity of anemia (N Engl J Med. 2020 Jan 9. 382(2):140-151).

“Patients with anemia and lower-risk...[MDS] in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions,” explained Pierre Fenaux, MD, PhD, Service d'Hématologie Séniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, France, and colleagues.

“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,” they added.

This led Dr Fenaux and colleagues to conduct a double blind, placebo-controlled phase 3 study exploring luspatercept in this patient population. The trial enrolled 229 patients with very low- to intermediate-risk MDS. Of which, 153 patients were randomly assigned to receive luspatercept (dosage of 1.0-1.75 mg/kg of body weight) or placebo every 3 weeks.

The primary end point of the study was transfusion independence for 8 weeks or longer during weeks 1-24. A secondary endpoint was transfusion independence for 12 weeks or longer that was assessed during weeks 1-24 as well as weeks 1-48.

In the luspatercept arm, 38% of patients achieved transfusion independence for 8 weeks or longer compared to 13% of patients in the placebo arm.

Additionally, transfusion independence for 12 weeks or longer was achieved by 28% of patients in the luspatercept arm compared to 8% of patients in the placebo arm for weeks 1-24; and 33% of the luspatercept arm versus 12% for weeks 1-48 (P<0.001 for all comparisons).

The most common adverse events associated with luspatercept were fatigue, diarrhea, asthenia, nausea, and dizziness.

“Luspatercept reduced the severity of anemia in patients with lower-risk...[MDS] 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,” concluded Dr Fenaux and colleagues.—Kaitlyn Manasterski