Luspatercept as Novel Standard of Care for ESA-Naive Patients With Transfusion-Dependent, Lower-Risk MDS
Primary Analysis Results from the Phase 3 COMMANDS Trial
Primary Analysis Results from the Phase 3 COMMANDS Trial
According to primary analysis results from the COMMANDS study, luspatercept treatment demonstrates a new standard of care for erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes (MDS).
“The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anemia in ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes,” stated first study author Matteo Giovanni Della Porta, MD, IRCCS Humanitas Research Hospital, Milan, Italy, and colleagues. Now, Della Porta and colleagues report primary analysis results.
This phase 3, open label, randomized, controlled trial was conducted at 142 sites in 26 countries. Eligible participants included those aged 18+ years, with very low-risk, low-risk, or intermediate-risk (as defined by the Revised International Prognostic Scoring System) MDS, who were ESA-naive and transfusion-dependent, and had a serum erythropoietin concentration of less than 500 U/L. The measured primary end point was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean hemoglobin increase of at least 1.5 g/dL (weeks 1 to 24), evaluated in the intention-to-treat (ITT) population. The safety population included all patients who received at least 1 dose of treatment.
Eligible patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration and ring sideroblast status, and randomly allocated on a 1-to-1 basis to receive luspatercept (1 to 1.75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450 to 1,050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80,000 IU) for at least 24 weeks.
Between January 2, 2019, and September 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to the luspatercept group and 181 (50%) to the epoetin alfa group. The median follow-up for the primary end point was 17.2 months (10.4 to 27.7) for the luspatercept cohort and 16.9 months (10.1 to 26.6) for the epoetin alfa cohort. Results demonstrated a significantly greater proportion of patients in the luspatercept arm reached the primary end point (110 [60%] vs 63 [35%]; common risk difference on response rate 25.4% [95% [confidence interval] CI, 15.8 to 35]; P < 0.0001).
In the measured safety profile, investigators noted the most common grade 3 to 4 treatment-related adverse events occurring among luspatercept patients (n = 182) were hypertension (19 [10%] patients), anemia (18 [10%]), pneumonia (10 [5%]), syncope (10 [5%]), neutropenia (9 [5%]), thrombocytopenia (8 [4%]), dyspnea (8 [4%]), and MDS (6 [3%]). The most common adverse events among epoetin alfa patients (n=179) were anemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), MDS (10 [6%]), hypertension (8 [4%]), iron overload (7 [4%]), and COVID-19 pneumonia (6 [3%]).
The most common serious treatment-related adverse events in both groups were pneumonia (9 [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (8 [4%] luspatercept recipients and 10 [6%] epoetin alfa recipients). It was recorded that 1 death occurred due to acute myeloid leukemia (AML) that was luspatercept-related and was reported at the interim analysis.
“Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes,” concluded Dr Della Porta and colleagues.
“Significantly more patients had red blood cell transfusion independence and hematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups,” they added.
Source:
Della Porta M, Garcia-Manero G, Santini V, et al. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): Primary analysis of a phase 3, open-label, randomized, controlled trial. Lan Hem. Published online July 19, 2024. doi: 10.1016/S2352-3026(24)00203-5
