Dr Amanam on the Real-World Efficacy of First-Line Luspatercept vs Erythropoiesis-Stimulating Agents in Lower-Risk MDS

"We think that what we’ve seen in the COMMANDS trial in terms of survival benefit—and how that translates into the real-world setting—clearly demonstrates that luspatercept is a highly effective therapy for these patients."

Idoroenyi Amanam, MD, an assistant professor in the Division of Leukemia in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, discussed findings from a real-world study of first-line luspatercept-aamt (Reblozyl) compared with erythropoiesis-stimulating agents (ESAs) in patients with lower-risk myelodysplastic syndromes (MDS), highlighting clinically meaningful improvements in transfusion independence and hemoglobin response.

In a retrospective United States–based cohort study, 360 patients with lower-risk MDS were identified, including 186 who initiated luspatercept and 174 who received ESAs in the first-line setting. Among these, 236 patients (luspatercept, n = 119; ESAs, n = 117) had evaluable data for hemoglobin levels and red blood cell (RBC) transfusions during the first 6 months of treatment and were included in the primary analysis. The composite end point was defined as achieving or maintaining RBC transfusion independence for at least 12 weeks alongside a hemoglobin level increase of at least 1.5 g/dL from baseline at any time during the first 6 months of index treatment.

Of the eligible population, 63.0% of patients treated with luspatercept met the composite end point, compared with 35.9% of those receiving ESAs (P < .001). After adjusting for baseline variables, such as International Prognostic Scoring System (IPSS)/Revised IPSS classification, serum erythropoietin levels, ring sideroblast status, and transfusion burden, the adjusted odds ratio for luspatercept was 3.26 (95% CI, 1.73-6.15), indicating a more than threefold increased likelihood of response relative to that with ESAs.

According to Amanam, these findings reinforce luspatercept’s role as a preferred first-line therapy in lower-risk MDS, particularly in patients with anemia and transfusion dependence. He noted that these data align with prior controlled trial findings, including those from the phase 3 COMMANDS trial (NCT03682536), and provide additional evidence of luspatercept’s benefit in routine clinical practice.