In the phase 3 COMMANDS trial (NCT03682536), luspatercept-aamt demonstrated superiority against epoetin alfa in the treatment of anemia in adults with erythropoiesis‑stimulating agents (ESA)-naïve transfusion-dependent lower‑risk myelodysplastic syndromes (LR‑MDS), according to interim efficacy and safety results reported at the 11th Annual Meeting of the Society of Hematologic Oncology (SOHO 2023).
As noted by presenter Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center in Houston, the findings from this open-label study led to the US Food and Drug Administration’s approval of luspatercept (Reblozyl®) for this patient population on August 28, 2023.
The trial included 356 adults with endogenous serum erythropoietin (sEPO) levels under 500 U/L who were randomized 1:1 to receive luspatercept (1.0-1.75 mg/kg) every 3 weeks or epoetin alfa (450-1050 IU/kg) weekly for at least 24 weeks and stratified by baseline red blood cell (RBC) transfusion burden, baseline sEPO, and ring sideroblast (RS) status. The median age of patients in each group was 74 years (range, 46-93) and 75 years (range, 33-91), respectively.
The median duration of treatment was 41.6 weeks in the luspatercept arm and 27 weeks in the epoetin alfa arm.
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In the luspatercept group, 58.5% of patients achieved RBC transfusion independence (RBC-TI) for 12 or more weeks, with a concurrent mean hemoglobin increase of at least 1.5 g/dL (the primary endpoint), compared to 31.2% of patients in the epoetin alfa group (P <.0001).
Luspatercept also showed more favorable results in secondary outcomes, with greater hematologic improvement in erythroid responses of 8 weeks or more (74.1% vs 51.3%; P <.0001), RBC‑TI within 24 weeks (47.6% vs 29.2%; P =.0006), and RBC-TI at 12 weeks or more (66.7% vs 46.1%; P =.0002) compared to epoetin alfa.
In addition, luspatercept demonstrated a longer median duration of RBC-TI compared to epoetin alfa (126.6 vs 77 weeks; hazard ratio, 0.456; 95% CI, 0.260-0.798) and across subgroups including RS-positive and RS-negative patients.
Treatment-emergent adverse events were reported in 92.1% of patients in the luspatercept group and 85.2% of those in the epoetin alfa group. Treatment discontinuation occurred in 44% of the luspatercept group vs 60% of the epoetin alfa group, most commonly for lack of efficacy (15.7% vs 32.4%, respectively).
On-treatment progression to acute myeloid leukemia (AML) was observed in 0.6% of each group, and overall AML progression rates were 2.2% with luspatercept and 2.8% with epoetin alfa. Progression to higher-risk MDS occurred in 2.8% of luspatercept-treated patients vs 4% of epoetin alfa-treated patients.
The groups had similar death rates during treatment (6.2% for luspatercept and 6.8% for EA) and overall (18% vs 18.2%, respectively).
“We believe that luspatercept provides clinical benefit regardless of subgroup and baseline mutational burden, and therefore… this [will become] the standard of care for the majority of our patients with lower-risk disease with anemia that are transfusion-dependent,” Dr. Garcia-Manero stated in the presentation.
References
Garcia-Manero G, Platzbecker U, Santini V, et al. Luspatercept versus epoetin alfa (EA) for treatment of anemia in patients with erythropoiesis-stimulating agent (ESA)-naïve lower-risk myelodysplastic syndromes (LR-MDS) requiring red blood cell (RBC) transfusions: data from the phase III COMMANDS study. 11th Annual Meeting of the Society of Hematologic Oncology (SOHO 2023). Houston, Texas. September 6, 2023. Abstract MDS-157.
FDA approves luspatercept-aamt as first-line treatment for adult patients with lower-risk MDS and anemia who may require transfusions. The ASCO Post. Published August 29, 2023. Accessed September 9, 2023.
