Patient-Reported Outcomes (PRO) of Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent (ESA)-Naïve, Transfusion-Dependent (TD), Lower-Risk Myelodysplastic Syndromes (LR-MDS): Results from the Phase 3 COMMANDS Study
Authors: Oliva Esther Natalie , Platzbecker Uwe , Della Porta Matteo Giovanni , Garcia-Manero Guillermo , Santini Valeria , Fenaux Pierre , Shortt Jake , Komrokji Rami S. , Pelligra Christopher , Guo Shien , Lord-Bessen Jennifer , Xiao Hong , Yucel Aylin , Miteva Dimana , Rose Shelonitda , Kreitz Sandra , Sekeres Mikkael A. , Zeidan Amer M. 
Published: December 2023

Background: For symptomatic anemia in patients with LR-MDS, supportive treatment with erythropoietin stimulating agents (ESAs), such as epoetin alfa, remains the current standard of care, which has limited and transient effect. The phase 3, open-label, randomized, controlled COMMANDS study demonstrated that luspatercept significantly improved the rate of transfusion independence and hemoglobin levels, when compared to epoetin alfa in ESA-naïve and transfusion-dependent (TD) patients with LR-MDS (Platzbecker U, et al. Lancet. 2023;S0140-6736(23)00874-7).

Objective: The objective of this interim analysis was to assess the effect of luspatercept versus epoetin alfa on patient-reported outcome (PRO) using data from the first 24 weeks of the COMMANDS study.

Methods: In COMMANDS, 356 patients were randomized 1:1 to luspatercept (Q3W) or epoetin alfa (QW). PROs, as one of the secondary objectives, were assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire.The EORTC QLQ-C30 was assessed on Day 1 prior to the first dose (baseline) and every 6 weeks thereafter; the FACT-An was administered at baseline, weekly for 3 weeks, and then every 3 weeks thereafter. Time to sustained improvement on domains of the EORTC QLQ-C30 and FACT-An was assessed between treatment arms using a stratified Cox proportional hazards regression model. Sustained improvement was defined as improvement from baseline ≥ pre-specified responder definition, sustained for at least 42 days through Week 25 Day 1 (W25D1). Overall treatment tolerability, assessed by the FACT-An item GP5 (“I am bothered by side effects of treatment”), was descriptively summarized at W25D1 by treatment arm. All analyses were conducted on the respective PRO-evaluable populations for each instrument, including patients who had completed the assessment at baseline and at least one post-baseline visit, unless otherwise specified.

Results: The EORTC QLQ-C30 evaluable population consisted of 150 and 144 patients randomized to luspatercept and epoetin alfa, respectively (median age 74.5 years and 54% male). Population sizes were similar for other PRO measures. Demographics, disease characteristics, and PRO domain scores at baseline were generally comparable between treatment arms. Completion rates of PRO assessments were moderately high for both arms (approximately 70-90%) through the W25D1 visit. Luspatercept resulted in a higher probability of sustained improvement through W25D1 in almost all domains of the EORTC QLQ-C30 and FACT-An compared to epoetin alfa, with significant differences (nominal p-value &lt;0.05) in dyspnea (hazard ratio [HR] [95% confidence interval]: 3.18 [1.03, 9.81]) and 7 other domains of the EORTC QLQ-C30 (role functioning, cognitive functioning, pain, insomnia, appetite loss, constipation, and financial difficulties). Patients in both arms experienced similar overall treatment tolerability, with &gt;67% of all patients still on treatment reporting to be “not at all” bothered by treatment side effects through W25D1.

Conclusions: The findings from these interim PRO analyses indicate that treatment with luspatercept increased sustained improvement across quality-of-life domains when compared to epoetin alfa. Luspatercept was also found to be well-tolerated by the majority of patients. All of these PRO findings further support the benefits of luspatercept in ESA-naïve and TD patients with LR-MDS.