Real-World Data Favors Luspatercept Over ESAs for Lower-Risk MDS

Frontline luspatercept demonstrates superior efficacy compared with erythropoiesis-stimulating agents (ESA) in patients with lower-risk myelodysplastic syndromes (MDS), according to a study presented at the 2025 American Society of Clinical Oncology Annual Meeting.

Idoroenyi Amanam, MD, of the City of Hope Cancer Center, and colleagues reported interim data from an ongoing, retrospective medical records review of 46 patients (median age, 67.7 years) who received luspatercept and 57 patients (median age, 62.9 years) who received ESAs for lower-risk MDS as defined by the International Prognostic Scoring System/Revised International Prognostic Scoring System (IPSS/IPSS-R).

Dr. Amanam and colleagues reported patient characteristics and changes in hemoglobin (Hb) and red blood cell (RBC) transfusion requirements during the first six months of treatment, with a median follow-up of 7.9 months for luspatercept and 8.4 months for ESAs.

As defined by the IPSS/IPSS-R, 21.7% of patients in the luspatercept group and 8.8% of patients in the ESA group had intermediate-1/intermediate risk status. 93.5% of patients in the luspatercept group and 68.4% of patients in the ESA group had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. Of patients with ring sideroblasts (RS), 23 of 37 (62.2%) patients receiving luspatercept and 28 of 39 (71.8%) patients receiving ESAs were RS negative.

In the first 6 months of treatment, 89.1% of patients in the luspatercept group and 56.1% of patients in the ESA group achieved an Hb increase of at least 1.5 g/dL. Among those who were RBC transfusion-dependent at baseline, 91.7% of patients in the luspatercept group achieved RBC transfusion-independence, compared with 71.4% of patients in the ESA group in the first 3 months.

“This analysis corroborates the results of the COMMANDS trial and demonstrates the favorable [real-world] effectiveness of [frontline luspatercept] vs [frontline] ESA for anemia treatment in LR-MDS,” wrote Dr. Amanam and colleagues.