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: Anemia; Epoetin alfa; Erythroid-stimulating agents; Luspatercept; Myelodysplastic syndromes; Transfusion-independence.
Myelodysplastic syndromes (MDS) are a group of blood disorders, where the bone marrow fails to make enough healthy blood cells. MDS is also considered a blood cancer. Patients who have lower-risk MDS (LR-MDS) have a lower chance of progressing to more serious conditions, like high-risk MDS or acute myeloid leukemia. Most patients with LR-MDS have anemia (low red blood cells [RBC]) and need frequent RBC transfusions. Erythropoiesis-stimulating agents (ESAs), like epoetin alfa, are commonly used to treat anemia. However, ESAs may not be as effective in all patients and the effects may not last as long. The COMMANDS trial looked at patients with LR-MDS and compared 2 treatments, luspatercept and epoetin alfa. The aim was to see which treatment could help patients avoid transfusions for a longer time, or be “transfusion-free.” The results showed that there were more patients on luspatercept who were transfusion-free, compared with epoetin alfa, at both the 1-year and the 1.5-year timepoints. These results were similar across different patient subgroups, including patients with specific genetic mutations. Patients treated with luspatercept and epoetin alfa had similar rates of side effects, which decreased over time. Additionally, the risk of progression to more serious conditions was low and similar between the two groups. In conclusion, luspatercept helped patients with LR-MDS avoid transfusions for over 1.5 years. This supports the use of luspatercept as a first-choice treatment in patients with LR-MDS.
© 2025. The Author(s).