ASCO 2025: Clinical Efficacy From the COMMANDS Trial for Luspatercept in Lower-Risk MDS

Video content above is prompted by the following:

The long-term follow-up results from the COMMANDS trial, presented at American Society of Clinical Oncology (ASCO) 2025 with median follow-up of 2.5 years, demonstrated sustained efficacy and tolerability of luspatercept compared with erythropoiesis-stimulating agents (ESAs) in patients with lower-risk myelodysplastic syndrome (MDS). Approximately 22% of patients remained on luspatercept vs 10% on ESAs, with 85% of luspatercept patients requiring at least 1 dose escalation during treatment. This finding has important clinical implications, as patients should be counseled that the medication requires time to work and dose adjustments are commonly needed throughout the treatment journey.

Updated efficacy outcomes showed impressive durability favoring luspatercept across multiple measures: 76% vs 56% achieved red blood cell transfusion independence for 12 weeks or longer, median duration of longest transfusion independence was 127 vs 87 weeks, and median cumulative duration of transfusion independence was 150 vs 95 weeks. These results demonstrate that luspatercept patients maintain responses approximately 1 year longer than ESA patients, with continued durable responses that reinforce the drug’s clinical value in managing lower-risk MDS.

The most significant finding was the trend toward improved overall survival, with median overall survival not reached for luspatercept vs 46 months for ESAs in the intention-to-treat population. This survival trend persisted across subgroups regardless of ring sideroblast status, baseline erythropoietin level, or transfusion burden. Notably, disease progression rates were low and similar between groups (4%-5% progressed to acute leukemia), suggesting the survival benefit may not be simply attributed to transfusion independence or disease progression prevention, indicating luspatercept may have additional mechanisms beyond erythroid maturation that warrant further investigation.