Luspatercept Reduces Transfusions, Boosts Hemoglobin in ESA-Naïve LR-MDS

The COMMANDS study explored treatment for anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS), particularly those who had not previously received erythropoiesis-stimulating agents (ESAs).

The study, which was presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology in Houston, Texas, compared the efficacy of luspatercept, a novel erythroid maturation agent, with that of epoetin alfa (EA) in ESA-naive LR-MDS patients requiring regular red blood cell (RBC) transfusions. Eligible patients included adults (≥18 years) with less than 5% bone marrow blasts, with or without ring sideroblasts, and with endogenous serum erythropoietin levels below 500 U/L.

Participants were randomly assigned (1:1) to receive either luspatercept (1.0–1.75 mg/kg every three weeks) or EA (450–1050 IU/kg weekly) for a minimum of 24 weeks. As of March 31, 2023, the results demonstrated a significant advantage with luspatercept compared with EA. A greater proportion of patients treated with luspatercept (83%) achieved a reduction of 50% or more in RBC transfusion needs over a 12-week period compared with those receiving EA (66.9%) (P=.0002). Additionally, the median duration of this reduction was notably longer with luspatercept (130 weeks) than with EA (77 weeks) (P=.0004).

Luspatercept Treatment in Lower-Risk MDS

Luspatercept efficacy was consistent across patients with varying levels of baseline transfusion burden. Among those requiring fewer than four RBC units per 8 weeks at baseline, 89% of luspatercept-treated patients achieved the reduction target, compared with 73.9% of those receiving EA. For those needing four or more RBC units per 8 weeks, the rates were 71.9% and 55.7% for luspatercept and EA, respectively. Furthermore, patients treated with luspatercept experienced a longer median time to their next RBC transfusion (155 days) compared with EA (42 days) (P<.0001).

The study also highlighted that more patients treated with luspatercept achieved durable responses in terms of RBC transfusion independence and mean hemoglobin increases. Specifically, 74.2% of luspatercept patients showed a hemoglobin increase of at least 1.5 g/dL, versus 52.5% of those treated with EA (P<.0001). The cumulative duration of response episodes was longer for luspatercept patients (147.9 weeks) compared with those on EA (95.1 weeks) (P=.0067).

These findings suggest that luspatercept is a more effective option than EA for reducing transfusion dependency and improving hemoglobin levels in ESA-naive patients with LR-MDS-related anemia, offering more durable benefits. The results support its consideration as a preferred treatment in this patient population.

Reference

Zeidan AM, Platzbecker U, Della Porta MG, et al. Clinical benefit of luspatercept treatment in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)-naïve patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) in the COMMANDS trial. Abstract #MDS-166. Presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology. September 4-7, 2024; Houston, Texas.