COMMANDS: Luspatercept Boosts Survival in ESA-Naïve MDS

Treatment with luspatercept in patients with first-line, erythropoiesis-stimulating agent (ESA)-naïve lower-risk myelodysplastic syndrome (MDS) achieved more durable responses compared with epoetin alfa, according to updated results from the phase 3 COMMANDS trial. Results also showed a trend toward overall survival (OS) advantage for luspatercept-treated patients, and no new safety concerns arose.

Valeria Santini, MD, chair of the Myelodysplastic Syndromes Unit at the University of Florence in Italy, presented the results during a session on prognostication and innovative treatment in MDS at the EHA 2025 Congress.

“This is the first time that we can show a significant advantage in terms of overall survival in patients with lower-risk MDS, transfusion dependency, receiving luspatercept versus epoetin alpha,” said Dr. Santini, during her presentation.

Median follow-up for the current analysis was 29.0 months in the luspatercept arm and 27.1 months in the epoetin alfa arm. Among the 182 patients treated with luspatercept, the median OS was not reached, when compared with 46.7 months in the epoetin alfa arm (HR, 0.86; 95% CI, 0.60-1.24).

The 3-year OS rates were 63.8% in the luspatercept-treated population versus 62.2% in the epoetin alfa population. At 4.5 years, the OS rates were 58.9% versus 41.8%, respectively. The signal for OS improvement with luspatercept versus epoetin alfa was similar in the subgroups evaluated in the study.

Dr. Santini stated: “There was a clear trend of an advantage of survival in patients treated with luspatercep. The median overall survival for the luspatercept group is not reached, [while] the median survival for the group treated with epoetin alfa [was] 46 [months].”

Red blood cell transfusion independence (RBC-TI) more than or 12 weeks was shown in 76.4% of those treated with luspatercept versus 55.8% of those treated with epoetin alfa.

“The median duration of the transfusion independence is 126 weeks versus 86 weeks… very significant prolongation,” said Dr. Santini.

There was also a 187.3-week median cumulative duration of RBC-TI more than or 12 weeks in the luspatercept compared with the epoetin alfa arm and had a median duration of 94.9 weeks  (HR, 0.51; 95% CI, 0.34-0.77).

With 24.7% of the luspatercept remaining on treatment at data cutoff versus 11.2% of the epoetin alfa arm, dose escalations were rare. Specifically, 84.6% of the luspatercept arm versus 82.7% of the epoetin alfa group.

According to Dr. Santini and colleagues, longer follow-up is necessary to confirm these updated results from the COMMANDs trial.

“Even with a follow-up of more than two and a half years, luspatercept still continues to improve response rate, longer duration of response, and significantly more patients achieve transfusion independence longer than 12 weeks.”