Dr Garcia-Manero on Luspatercept in Lower-Risk MDS

Guillermo Garcia-Manero, MD, professor, chief, Section of Myelodysplastic Syndromes, deputy chair, Translational Research, fellowship program director, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses key efficacy and safety findings from the phase 3 COMMANDS trial (NCT03682536) of luspatercept-aamt (Reblozyl) vs epoetin alfa in patients with lower-risk myelodysplastic syndrome.

The COMMANDS trial included patients who were naïve to erythropoiesis-stimulating agents and required red blood cell (RBC) transfusions to treat anemia with LR-MDS. Patients were randomly assigned to receive either luspatercept at 1.0 mg/kg subcutaneously every 3 weeks with titration up to 1.75 mg/kg or epoetin alfa at 450 IU/kg subcutaneously every week with titration up to 1050 IU/kg. The primary end point of this trial was RBC transfusion independence for at least 12 weeks with a concurrent mean hemoglobin increase of at least 1.5 g/dL.

In the intention-to-treat population, 58.5% of patients in the luspatercept arm (n = 147) achieved the primary end point vs 31.2% of patients in the epoetin alfa arm (n = 154). The mean time to first RBC transfusion was also prolonged with luspatercept, at 168 weeks compared with 42.0 weeks with epoetin alfa.

The 2 arms of this trial had similar safety profiles because both luspatercept and epoetin alfa are modulating cytokines with no expected severe toxicities, Garcia-Manero says. Any-grade treatment-emergent adverse effects (TEAEs) occurred in 92.1% of patients in the luspatercept arm and 85.2% of patients in the epoetin alfa arm. Additionally, the rates of disease transformation and death were similar between the 2 arms, Garcia-Manero notes. Progression to high-risk MDS occurred in 2.8% and 4.0% of patients in the luspatercept and epoetin alfa arms, respectively, and progression to acute myeloid leukemia occurred in 2.2% and 2.8% of patients, respectively. On-treatment deaths occurred in 6.2% and 6.8% of patients in the luspatercept and epoetin alfa arms, respectively, and 32 total deaths occurred in each arm.

Luspatercept appears to be safe and significantly more effective than epoetin alfa, Garcia-Manero concludes.

Disclosures: Dr Garcia-Manero reports honoraria from Abbvie, Acceleron Pharma, Astex Pharmaceuticals, Bristol-Myers Squibb/Celgene, Curis, Genentech, Gilead Sciences, and Novartis; consulting or advisory roles with Acceleron Pharma, Astex Pharmaceuticals, and Bristol-Myers Squibb; and research funding from Abbvie, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Curis, Genentech, Gilead Sciences, and Novartis.