Long-Term Transfusion Independence with Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes in the COMMANDS Trial

Authors

Guillermo Garcia-Manero
Valeria Santini
Amer M Zeidan
Rami S Komrokji
Veronika Pozharskaya
Shelonitda Rose
Karen Keeperman
Yinzhi Lai
Sameer Kalsekar
Barkha Aggarwal
Dimana Miteva
David Valcárcel
Pierre Fenaux
Jake Shortt
Matteo Giovanni Della Porta
Uwe Platzbecker

Publication Date

7-1-2025

Journal

Advances in Therapy

DOI

10.1007/s12325-025-03208-5

PMID

40377899

PMCID

PMC12182481

PubMedCentral® Posted Date

5-16-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: The efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.

Methods: Eligible patients aged ≥ 18 years, with ESA-naive, RBC TD LR-MDS were randomized 1:1 to receive luspatercept (1.0 mg/kg, titration to 1.75 mg/kg permitted) or epoetin alfa (450 IU/kg, titration to 1050 IU/kg). Disease assessment was carried out at week 24 (day 169) and every 24 weeks thereafter. Treatment continued until disease progression, lack of clinical benefit, unacceptable toxicity, or consent withdrawal.

Results: At data cutoff (September 22, 2023; median follow-up: luspatercept 21.4 months, epoetin alfa 20.3 months), a greater proportion of patients treated with luspatercept (n = 182) versus epoetin alfa (n = 181) achieved a longest single RBC-TI period ≥ 1 year (44.5% vs. 27.6%; P = 0.0003) and ≥ 1.5 years (30.2% vs. 13.8%; P < 0.0001). Higher rates of RBC-TI ≥ 1.5 years with luspatercept over epoetin alfa were consistent across all prespecified subgroups, including patients with ring sideroblast-negative status and low baseline serum erythropoietin. Longer cumulative RBC-TI response [sum of all durations of RBC-TI for ≥ 12 weeks; week 1 to end of treatment (95% CI)] was observed with luspatercept [154.7 weeks (118.4-NR)] versus epoetin alfa [91.1 weeks (73.1-123.9)]. Rates of treatment-emergent adverse events, including asthenia and hypertension, generally decreased over time in both arms. Progression rates to high-risk MDS and acute myeloid leukemia were similarly low (< 5%) in both treatment arms.

Conclusions: These data demonstrated sustained, durable clinical benefit across subgroups and support luspatercept as the treatment of choice for anemia in patients with LR-MDS who are TD and ESA-naive.

Trial registration number: NCT03682536.

Keywords

Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Activin Receptors, Type II, Anemia, Blood Transfusion, CD47 Antigen, Epoetin Alfa, Erythrocyte Transfusion, Hematinics, Immunoglobulin Fc Fragments, Myelodysplastic Syndromes, Recombinant Fusion Proteins, Anemia, Epoetin alfa, Erythroid-stimulating agents, Luspatercept, Myelodysplastic syndromes, Transfusion-independence

Published Open-Access

yes

Recommended Citation

Garcia-Manero, Guillermo; Santini, Valeria; Zeidan, Amer M; et al., "Long-Term Transfusion Independence with Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes in the COMMANDS Trial" (2025). Faculty, Staff and Student Publications. 4406.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4406