Luspatercept-aamt (Reblozyl) sustained durable red blood cell transfusion independence (RBC-TI) and produced a favorable overall survival (OS) trend vs epoetin alfa in erythropoiesis-stimulating agent (ESA)–naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes (MDS), according to updated data from the phase 3 COMMANDS trial (NCT03682536) presented at the
At a data cutoff of October 9, 2025, and a median follow-up of 35.9 months in the luspatercept arm and 30.8 months in the epoetin alfa arm, the median OS was not reached with luspatercept vs 46.0 months with epoetin alfa (HR, 0.781; 95% CI, 0.559-1.092; P = .1485); the difference did not reach statistical significance. The 5-year OS rate was 54% with luspatercept compared with 42% with epoetin alfa.
RBC-TI for at least 12 weeks (weeks 1 through end of treatment) was achieved by 76% of patients in the luspatercept arm compared with 56% in the epoetin alfa arm. The median duration of the longest single RBC-TI response was 127 weeks with luspatercept vs 87 weeks with epoetin alfa, and the median cumulative duration of RBC-TI lasting at least 12 weeks was 150 weeks vs 95 weeks, respectively. The OS trend favoring luspatercept was consistent across subgroups, including analyses stratified by ring sideroblast status, baseline endogenous erythropoietin level, and baseline transfusion burden.
Longer-term responses also favored luspatercept, with RBC-TI sustained for at least 2.5 years reported in 25.3% of patients in the luspatercept arm vs 10.5% in the epoetin alfa arm. A mean hemoglobin increase of at least 1.5 g/dL was observed in 80.2% vs 58.6% of patients, respectively, with respective median durations of 72.9 weeks and 47.9 weeks.
“This long-term analysis of COMMANDS supports the durable clinical benefit of luspatercept and reinforces its use as a first-line option for anemia in ESA-naive patients with transfusion-dependent, lower-risk MDS,” lead study author Valeria Santini, MD, of the University of Florence in Florence, Italy, and colleagues wrote in a poster presentation of the data.
Prior data from COMMANDS
COMMANDS was a global, phase 3, open-label, randomized controlled trial evaluating luspatercept vs epoetin alfa as first-line treatment for anemia in ESA-naive patients with lower-risk MDS.1 Eligible patients were 18 years of age or older with very low–, low–, or intermediate-risk MDS per Revised International Prognostic Scoring System criteria, were transfusion dependent, and had a serum erythropoietin level below 500 U/L.
Patients were randomly assigned 1:1 to receive luspatercept initiated at 1.0 mg/kg subcutaneously every 3 weeks and titratable up to 1.75 mg/kg, or epoetin alfa initiated at 450 IU/kg subcutaneously once per week and titratable up to 1050 IU/kg.
The primary end point was RBC-TI for at least 12 weeks with a concurrent mean hemoglobin increase of at least 1.5 g/dL during weeks 1 through 24. OS was assessed as a secondary end point; the trial was not powered to demonstrate an OS difference.
With longer follow-up, the safety profile of luspatercept remained consistent with that reported in earlier COMMANDS analyses, and no new safety signals were identified. Investigators reported no unexpected treatment-emergent adverse effects with extended exposure.
Rates of disease progression, including progression to higher-risk MDS or acute myeloid leukemia (AML), remained low across the study population. In the luspatercept arm, the rates of progression to higher-risk MDS and AML were 3.3% and 4.9%, respectively. In the control arm, these respective rates were 7.3% and 5.5%.
In total, 36.3% of patients in the luspatercept arm had died vs 43.0% in the control arm. The most common causes of death included neoplasms (luspatercept, 8.2%; epoetin alfa, 11.2%), infections/infestations (6.6%; 8.4%), and cardiac disorders (4.9%; 6.1%).
