Primary analysis finds luspatercept reduces transfusion dependence in lower-risk MDS

Luspatercept is more effective than epoetin alfa in achieving transfusion independencin anemia patients with lower-risk myelodysplastic syndromes (MDS), according to a primary analysis of the phase III COMMANDS trial published in The Lancet Haematology.

In the COMMANDS trial, conducted at 142 sites across 26 countries, 60% of patients receiving luspatercept achieved independence from red blood cell transfusions for at least 12 weeks with a significant rise in hemoglobin, compared with 35% of those treated with epoetin alfa.

The study enrolled 363  erythropoiesis-stimulating agent (ESA)-naive patients ages 18 and older who were dependent on transfusions due to lower-risk MDS. Participants were randomly assigned to either luspatercept, administered every three weeks, or epoetin alfa, administered weekly.

Both treatments showed similar safety profiles, though some variations in adverse events emerged. Among luspatercept recipients, the most common serious side effects included hypertension, anemia, and pneumonia, while epoetin alfa patients more frequently experienced neutropenia, iron overload, and COVID-19 pneumonia. One luspatercept-related death was reported, attributed to acute myeloid leukemia.

These results indicate that luspatercept provides a significant step forward in managing anemia for transfusion-dependent, lower-risk MDS patients, with benefits observed across various patient subgroups and the potential to enhance quality of life by reducing transfusion dependence, according to the investigators, led by Matteo Giovanni Della Porta, MD, of Humanitas University in Mexico.

“Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes,” the researchers wrote in the article. “Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups.”

Reference

R Della Porta MG, Garcia-Manero G, Santini V, et al. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024;11(9):e646-e658. doi:10.1016/S2352-3026(24)00203-5eference