EFFICACY AND SAFETY OF LUSPATERCEPT VERSUS EPOETIN ALFA IN ERYTHROPOIESIS-STIMULATING AGENT (ESA)-NAIVE PATIENTS WITH TRANSFUSION-DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS): FULL ANALYSIS OF THE COMMANDS TRIAL

Abstract

Introduction: We report the full analysis of the COMMANDS trial assessing efficacy and safety of luspatercept versus epoetin alfa (EA) in ESA-naive patients with LR-MDS. Methods: 363 patients (aged ≥18 y, with transfusion-dependent LR-MDS, serum erythropoietin <500 U/L) were randomized 1:1 to luspatercept or EA. Primary endpoint was achievement of red blood cell transfusion independence (RBC-TI) ≥12 wk with concurrent mean hemoglobin increase ≥1.5 g/dL (wk 1–24). Secondary endpoints included achievement of RBC-TI ≥12 and 24 wk, hematologic improvement–erythroid (HI-E) ≥8 wk (wk 1–24), RBC-TI ≥12 wk duration, and safety. Results: As of 31Mar2023, 110/182 (60.4%) luspatercept-treated versus 63/181 (34.8%) EA-treated patients achieved the primary endpoint (P<0.0001). Primary endpoint achievement favored luspatercept in most subgroups including region. Median (range) treatment duration was 51.3 (3–196) and 37.0 (1–202) wk for luspatercept versus EA. 68.1% and 48.6% of luspatercept- versus EA-treated patients, respectively, achieved RBC-TI ≥12 wk; 47.8% and 30.9% achieved RBC-TI 24 wk; 74.4% and 53.0% achieved HI-E ≥8 wk. Median (95% CI) duration of RBC-TI ≥12 wk was 128.1 wk (108.3–not estimable [NE]) with luspatercept versus 89.7 wk (55.9–157.3) with EA (HR, 0.534; Figure). 2.7% and 3.3% of luspatercept- and EA-treated patients, respectively, progressed to AML; 97.8% and 92.2% reported any-grade treatment-emergent adverse events (TEAEs); 58.5% and 49.2% reported grade 3/4 TEAEs. Death rates on- and post-treatment were similar between arms. Conclusions: RBC-TI duration and erythroid responses achieved with luspatercept were superior to EA. Luspatercept safety results were consistent with previous MDS studies.