CLINICAL BENEFIT of LUSPATERCEPT in TRANSFUSION-DEPENDENT, ERYTHROPOIESIS-STIMULATING AGENT-NAIVE PATIENTS with VERY LOW-, LOW-OR INTERMEDIATE-RISK MYELODYSPLASTIC SYNDROMES in the COMMANDS TRIAL.

Abstract

Background: There is an unmet need for an effective treatment (tx) that provides durable benefit for patients (pts) with anemia due to lower-risk myelodysplastic syndromes (LR-MDS). Aim(s): To report clinically meaningful responses to luspatercept tx in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)-naive pts with LR MDS in the COMMANDS trial (NCT03682536). Method(s): Eligible pts were >= 18 years of age, had LR-MDS with or without ring sideroblasts and < 5% bone marrow blasts, endogenous serum erythropoietin < 500 U/L, required red blood cell (RBC) transfusions (defined as 2-6 RBC units/8 weeks [wk] for >= 8 wk prior to randomization), and were ESA naive. Pts were randomized 1:1 to subcutaneous administration of luspatercept (1.0-1.75 mg/kg) once every 3 wk or epoetin alfa (450-1050 IU/kg) once weekly for >= 24 wk. New assessments of clinical benefit reported here include achievement and duration of >= 50% reduction in RBC units transfused over >= 12 wk and >= 24 wk (wk 1-end of tx [EOT]), transfusion burden (TB) on tx (wk 1-24), time to first transfusion, achievement and cumulative duration of all separate RBC transfusion independence (RBC-TI) >= 12 wk response episodes (wk 1-EOT), and mean hemoglobin (Hb) increase >= 1.5 g/dL over wk 1-24. Result(s): As of March 31, 2023, 151/182 (83.0%) pts treated with luspatercept and 121/181 (66.9%) pts treated with epoetin alfa achieved >= 50% reduction in RBC units transfused over >= 12 wk (wk 1-EOT; P = 0.0002), with median (95% confidence interval [CI]) durations of 130.0 (120.6-not evaluable [NE]) and 77.0 (54.9-123.1) wk, respectively (P = 0.0004). A greater proportion of luspatercept versus epoetin alfa pts achieved >= 50% reduction in RBC units transfused over >= 12 wk (wk 1-EOT), regardless of baseline (BL) TB: 105/118 (89.0%) pts treated with luspatercept versus 82/111 (73.9%) pts treated with epoetin alfa with BL TB < 4 RBC units/8 wk and 46/64 (71.9%) pts receiving luspatercept versus 39/70 (55.7%) pts receiving epoetin alfa with TB >= 4 RBC units/8 wk. Similarly, achievement of >= 50% reduction in RBC units transfused over >= 24 wk (wk 1-EOT) favored luspatercept over epoetin alfa (P < 0.0001; Figure), with median (95% CI) duration of 160.0 (135.0-NE) wk in the luspatercept arm and 117.4 (80.1-NE) wk in the epoetin alfa arm (P = 0.0011). The median (interquartile range) number of RBC units transfused during wk 1-24 of tx was 1.0 (0-5.0) in the luspatercept arm and 3.0 (0-8.0) in the epoetin alfa arm. The median (95% CI) time to first transfusion was 155.0 (80.0-266.0) days for luspatercept versus 42.0 (23.0-55.0) days for epoetin alfa pts (P < 0.0001). Among pts who achieved RBC-TI >= 12 wk (wk 1-24), 22/124 (17.7%) luspatercept pts versus 12/88 (13.6%) epoetin alfa pts achieved >= 2 separate RBC-TI >= 12 wk response episodes (ie, achieved RBC-TI >= 12 wk response, lost RBC-TI response, then later achieved RBC-TI again) during the entire tx period. The cumulative median (95% CI) duration of all response episodes (wk 1-EOT) was 147.9 (122.0-NE) wk in the luspatercept arm and 95.1 (73.1-NE) wk in the epoetin alfa arm (P = 0.0067). Mean Hb increase >= 1.5 g/dL over wk 1-24 was achieved by 135/182 (74.2%) luspatercept pts and 95/181 (52.5%) epoetin alfa pts (P < 0.0001). Summary/Conclusion: Significantly greater proportions of pts treated with luspatercept than with epoetin alfa achieved improvements in Hb levels, reduction in TB and RBC units transfused, and had durable RBC-TI responses. Luspatercept provided clinically meaningful outcomes, supporting its use as the preferred tx for ESA-naive pts with LR-MDS-associated anemia. (Figure present).