Luspatercept is more effective than epoetin alfa for treating anemia in patients with erythropoiesis-stimulating agent (ESA)-naïve, transfusion-dependent, lower-risk myelodysplastic syndromes (MDS), according to results from the phase 3 COMMANDS trial.
Luspatercept increased hemoglobin levels and allowed a greater proportion of patients to achieve durable transfusion independence. The median duration of response was nearly 1 year longer with luspatercept than with epoetin alfa.
Luspatercept is the first therapy to demonstrate superiority over an ESA in a head-to-head study and brings a paradigm shift in the treatment of lower-risk-MDS-associated anemia, according to study presenter Guillermo Garcia-Manero, MD, of MD Anderson Cancer Center in Houston.
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Dr Garcia-Manero presented these results at the ASCO Annual Meeting 2023.
The COMMANDS trial (ClinicalTrials.gov Identifier: NCT03682536) included 356 patients with ESA-naïve, transfusion-dependent, lower-risk MDS. They were randomly assigned to receive luspatercept (n=178) or epoetin alfa (n=178). Baseline characteristics were well balanced between the arms.
Patients in the luspatercept arm received a starting dose of 1.0 mg/kg (titration up to 1.75 mg/kg) once every 3 weeks. Patients in the epoetin alfa arm received a starting dose of 450 IU/kg (titration up to 1050 IU/kg) weekly. The median duration of treatment was 41.6 weeks in the luspatercept arm and 27.0 weeks in the epoetin alfa arm.
The primary endpoint was red blood cell (RBC) transfusion independence lasting at least 12 weeks with concurrent average hemoglobin increases of 1.5 g/dL or more within the first 24 weeks.
The primary endpoint was achieved in 58.5% of patients in the luspatercept arm and 31.2% of those in the epoetin alfa arm (P <.0001). A greater proportion of patients achieved the primary endpoint in the luspatercept arm across all subgroups except among patients without ring sideroblasts.
The median duration of response (RBC transfusion independence of 12 weeks or more) was 126.6 weeks in the luspatercept arm and 77.0 weeks in the epoetin alfa arm (hazard ratio, 0.456; 95% CI, 0.260-0.798). The median time to first RBC transfusion was 168.0 weeks and 42.0 weeks, respectively.
The proportion of patients with RBC transfusion independence lasting at least 24 weeks was 47.6% in the luspatercept arm and 29.2% in the epoetin alfa arm (P <.0006). RBC transfusion independence lasting at least 12 weeks occurred in 66.7% and 46.1% of patients, respectively (P <.0002).
The proportion of patients with hematologic improvement-erythroid response lasting at least 8 weeks was 74.1% in the luspatercept arm and 51.3% in the epoetin alfa arm (P <.0001).
Treatment discontinuation occurred in 43.8% of patients in the luspatercept arm and 59.7% of those in the epoetin alfa arm. In both arms, the most common reason for discontinuation was lack of efficacy (15.7% with luspatercept and 32.4% with epoetin alfa).
Treatment-emergent adverse events (TEAEs) occurred in 92.1% of patients in the luspatercept arm and 85.2% of those in the epoetin alfa arm.
The most common grade 3-4 hematologic TEAEs were anemia (7.3% with luspatercept and 6.8% with epoetin alfa), thrombocytopenia (3.9% and 0.6%, respectively), and neutropenia (3.9% and 5.7%). The most common grade 3-4 TEAEs of interest were dyspnea (3.9% and 1.1%) and thromboembolic events (2.8% and 0.6%).
Disclosures: This research was supported by Celgene, a subsidiary of Bristol Myers Squibb, and Acceleron Pharma, a subsidiary of Merck. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Garcia-Manero G, Platzbecker U, Santini V, et al. Efficacy and safety results from the COMMANDS trial: A phase 3 study evaluating luspatercept vs epoetin alfa in erythropoiesis-stimulating agent (ESA)-naive transfusion-dependent (TD) patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS). ASCO 2023. June 2-6, 2023. Abstract 7003.
