COMMANDS and ELEMENT-MDS Trials: Long-Term Analysis, Survival, Duration of Response, and Hemoglobin Levels

EP: 1.Early vs Late Onset of ESA in LR-MDS: Results From Phase 3 EPO-PRETAR Trial

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EP: 2.COMMANDS and ELEMENT-MDS Trials: Long-Term Analysis, Survival, Duration of Response, and Hemoglobin Levels

This presentation provided updated long-term data from a phase 3 trial comparing luspatercept with epoetin alfa in lower-risk patients with myelodysplastic syndromes (MDS) who were transfusion dependent and had low serum erythropoietin (EPO) levels (<500 mU/mL). Patients were randomly assigned to receive either luspatercept with dose escalation or standard-dose epoetin, with treatment continuing until disease progression or loss of clinical benefit. The primary end point was red blood cell transfusion independence (RBC-TI) for at least 12 weeks, along with a mean hemoglobin increase of ≥1.5 g/dL.

Luspatercept demonstrated superior efficacy, with significantly more patients achieving prolonged RBC-TI. Nearly 45% of patients in the luspatercept arm achieved at least 1 year of transfusion independence compared with 28% in the epoetin arm. Additionally, 32% on luspatercept maintained RBC-TI for at least 1.5 years, vs 14.6% with epoetin. The trend held across subgroups, including those with ring sideroblast–negative disease. Long-term follow-up showed a 5-year overall survival rate of 54% with luspatercept, compared with 42% with epoetin, though the HR (0.86) did not indicate a statistically significant difference.

Safety data showed that while treatment-emergent adverse events (TEAEs) were common in both arms, the majority were related to underlying MDS rather than the treatment itself. Around 33% of luspatercept-treated patients experienced treatment-related TEAEs, with no strong correlation between dose escalation and higher-grade toxicities. The ongoing ELEMENT-MDS trial, also highlighted briefly, is evaluating earlier intervention in non–transfusion-dependent patients using the same agents. This trial aims to determine whether initiating therapy before transfusion dependency can prevent progression and improve outcomes.