B04 | OVERALL SURVIVAL AND DURATION OF TRANSFUSION INDEPENDENCE FOR FIRST-LINE ERYTHROPOIESIS STIMULATING AGENT-NAIVE PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES TREATED WITH LUSPATERCEPT VS. EPOETIN ALFA: COMMANDS TRIAL

BACKGROUND: The phase 3 COMMANDS study (NCT03682536) showed that LUSPA improved red blood cell (RBC)-TI ≥12 wks with a concurrent hemoglobin increase of ≥1.5 g/dL in Wks 1 to 24 compared with EA and had durable clinical benefit in pts with ESA-naive TD LR-MDS. Here, we report updated OS and duration of RBC-TI. METHODS: Eligible pts (≥18 yrs; ESA-naive; RBC TD; very low/low/intermediate-risk MDS; serum erythropoietin [EPO] <500 U/L) were stratified by baseline (BL) RBC transfusion burden (TB), ring sideroblast (RS) status, and EPO level, and randomized 1:1 to receive LUSPA (1.0-1.75 mg/kg; SC Q3W) or EA (450-1050 IU/kg; SC QW) for ≥24 wks. Secondary endpoints included OS, duration of RBC-TI ≥12 wks, and safety. RESULTS: At cutoff (Nov 4, 2024), median follow up was 29.0 mos for LUSPA (n=182) and 27.1 mos for EA (n=181). In the ITT population, median OS was not reached (NR) for LUSPA and was 46.7 mos for EA (HR, 0.86; 95% CI, 0.60-1.24); 3-yr OS rates were 63.8% (LUSPA) and 62.2% (EA), and 4.5-yr OS rates were 58.9% and 41.8% (Figure). Among an OS analysis by stratification subgroups, similar trends were observed. Overall, RBC-TI ≥12 wks (Wk 1 to end of treatment [EOT]) was achieved by 76.4% and 55.8% of pts in the LUSPA vs EA arm, respectively. Median cumulative duration of RBC-TI ≥12 wks (sum of all durations of RBC-TI ≥12 wks episodes from Wk 1 to EOT) was 187.3 (95% CI, 119.6-NE) wks for LUSPA vs 94.9 (95% CI, 73.1-179.0) wks for EA (HR, 0.51; 95% CI, 0.34-0.77). Median duration of longest RBC-TI ≥12 wks period (from Wk 1 to EOT) was 126.6 (95% CI, 81.0-184.4) vs 86.7 (95% CI, 55.9-111.1) wks (HR, 0.64; 95% CI, 0.44-0.93). At cutoff, 24.7% and 11.2% of LUSPA and EA pts, respectively, were on treatment; 84.6% and 82.7% had ≥1 dose escalation. No new safety concerns emerged with longer follow up. Deaths occurred in both arms on- (10.4% vs 9.5%) and post-treatment (20.9% vs 26.3%). Progression to acute myeloid leukemia was comparable for LUSPA and EA pts (3.8% vs 4.4%). CONCLUSIONS: LUSPA treatment resulted in a clinically meaningful and statistically significant longer duration of response compared with EA. There was a positive OS trend compared with EA, which was consistent across all subgroups, and no new safety concerns. Longer follow up is required to confirm these data. These data continue to support LUSPA as treatment for anemia in first-line LR-MDS.