MDS-166 clinical benefit of luspatercept treatment in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)-naive patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) in the COMMANDS trial.

Abstract

Context: There is an unmet need for effective treatments that provide durable benefit for patients with anemia due to lower-risk (LR) MDS. Objective(s): To report clinically meaningful responses to luspatercept treatment in TD, ESA-naive patients with LR-MDS (COMMANDS; NCT03682536). Patient(s): Adults (>=18 years) with LR-MDS (with or without ring sideroblasts) and <5% bone marrow blasts requiring RBC transfusions, endogenous serum erythropoietin <500 U/L, ESA-naive. Intervention(s): Patients (randomized 1:1) received luspatercept (1.0-1.75 mg/kg) Q3W or epoetin alfa (EA; 450-1050 IU/kg) QW for >=24 weeks. Result(s): As of March 31, 2023, 151/182 (83.0%) luspatercept-treated and 121/181 (66.9%) EA-treated patients received >=50% fewer RBC units transfused over >=12 weeks (week 1 to end of treatment; P = .0002); median (95% CI) durations were 130.0 (120.6-not evaluable [NE]) and 77.0 (54.9-123.1) weeks, respectively (P = .0004). More luspatercept than EA patients achieved this level of reduction regardless of baseline transfusion burden: 105/118 (89.0%) luspatercept vs 82/111 (73.9%) EA patients requiring <4 RBC units/8 weeks and 46/64 (71.9%) luspatercept vs 39/70 (55.7%) EA patients requiring >=4 RBC units/8 weeks. Median (interquartile range) number of RBC units transfused (weeks 1-24) was 1.0 (0-5.0) for luspatercept and 3.0 (0-8.0) for EA. Median (95% CI) time to RBC transfusion after treatment initiation was 155.0 (80.0-266.0) days for luspatercept vs 42.0 (23.0-55.0) days for EA (P < .0001). Among patients who achieved RBC transfusion independence (RBC-TI) >=12 weeks (weeks 1-24), 22/124 (17.7%) luspatercept vs 12/88 (13.6%) EA patients achieved >=2 separate responses; cumulative median (95% CI) duration of all response episodes was 147.9 (122.0-NE) weeks for luspatercept and 95.1 (73.1-NE) weeks for EA (P = .0067). Mean hemoglobin increase >=1.5 g/dL (weeks 1-24) was achieved by 135/182 (74.2%) luspatercept and 95/181 (52.5%) EA patients (P < .0001). Conclusion(s): More luspatercept versus EA patients achieved hemoglobin level improvements, reductions in transfusion burden and RBC units transfused, and had durable RBC-TI responses, supporting luspatercept use as the preferred treatment for ESA-naive patients with LR-MDS-associated anemia. Acknowledgement: ©2024 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2024 ASCO Annual Meeting. All rights reserved.Copyright © 2024 Elsevier Inc.