Luspatercept Is Effective for ESA-Naïve, Transfusion-Dependent, Lower-Risk MDS

Patients with erythropoiesis-stimulating agent (ESA)-naïve, transfusion-dependent, lower-risk myelodysplastic syndrome (LR-MDS) had improved red blood cell transfusion independence (RBC-TI) and erythroid responses when treated with luspatercept compared with ESAs, according to the full results of the COMMANDS trial.

Results were presented by Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center in Houston, Texas, at the 65th ASH Annual Meeting and Exposition. They indicated that luspatercept could be a new standard of care for patients with transfusion-dependent LR-MDS.

The COMMANDS trial enrolled 182 patients with Revised International Prognostic Scoring System–defined LR-MDS with <5% bone marrow blasts and serum erythropoietin (sEPO) <500 U/L. Patients were randomly assigned to luspatercept or epoetin alfa. The primary endpoint was RBC-TI of 12 weeks or longer with a concurrent mean hemoglobin increase of at least 1.5 g/dL.

The primary endpoint was achieved by 60.4% of patients assigned to luspatercept compared with 34.8% of patients assigned to epoetin alfa (P<0.0001).

Response rates with luspatercept versus epoetin alfa were greater for patients with SF3B1-mutated and non-mutated disease, with baseline sEPO ≤200 U/L and with baseline sEPO >200 to <500 U/L, and greater for ring sideroblast–positive patients. There was no significant difference in response for ring sideroblast–negative patients.

Median duration of RBC-TI of 12 weeks or longer with luspatercept was 128.1 weeks compared with 89.7 weeks with epoetin alfa (hazard ratio=0.534).

Five patients in both arms progressed to acute myeloid leukemia. The majority of patients in both treatment arms experienced treatment-emergent adverse events of any grade. Grade 3 or 4 treatment-emergent adverse events occurred in 58.8% of patients assigned to luspatercept and 49.2% of patients assigned to epoetin alfa.

The rates of on-therapy and post-therapy deaths were similar for patients assigned to luspatercept or epoetin alfa.

Reference

Garcia-Manero G, Platzbecker U, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent (ESA)-naïve patients (Pts) with transfusion-dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS): full analysis of the COMMANDS trial. Abstract #193. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.