Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the MEDALIST Phase 3 Trial.

Esther Natalie Oliva,Ghulam J Mufti,Valeria Santini,Guillermo Garcia-Manero,Xianwei Ha,Weiqin Liao,George Zhang,Mikkael A Sekeres,Shien Guo,Derek Tang,Uwe Platzbecker,Rami S Komrokji,Jeevan K Shetty,Jay T Backstrom,Rodrigo Ito,Jennifer Lord-Bessen,Pierre Fenaux

doi:10.3390/jcm11010027

Abstract

Patients with myelodysplastic syndromes (MDS) often experience chronic anemia and long-term red blood cell transfusion dependence associated with significant burden on clinical and health-related quality of life (HRQoL) outcomes. In the MEDALIST trial (NCT02631070), luspatercept significantly reduced transfusion burden in patients with lower-risk MDS who had ring sideroblasts and were refractory to, intolerant to, or ineligible for prior treatment with erythropoiesis-stimulating agents. We evaluated the effect of luspatercept on HRQoL in patients enrolled in MEDALIST using the EORTC QLQ-C30 and the QOL-E questionnaire. Change in HRQoL was assessed every 6 weeks in patients receiving luspatercept with best supportive care (+ BSC) and placebo + BSC from baseline through week 25. No clinically meaningful within-group changes and between-group differences across all domains of the EORTC QLQ-C30 and QOL-E were observed. On one item of the QOL-E MDS-specific disturbances domain, patients treated with luspatercept reported marked improvements in their daily life owing to the reduced transfusion burden, relative to placebo. Taken together with previous reports of luspatercept + BSC reducing transfusion burden in patients from baseline through week 25 in MEDALIST, these results suggest luspatercept may offer a treatment option for patients that reduces transfusion burden while providing stability in HRQoL.

Highlights

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic neoplasms characterized by ineffective hematopoiesis, progressive cytopenias, and risk of progression to acute myeloid leukemia [1,2]
For patients who are refractory to erythropoiesis-stimulating agents (ESAs), anemia is commonly managed with frequent red blood cell (RBC) transfusions [2]
Treatment with RBC transfusions can provide transient relief in anemia-related symptoms, fatigue and dyspnea, which can be associated with short-term improvements in health-related quality of life (HRQoL) measures such as physical, role, and social functioning [11,12]

Summary

Introduction

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic neoplasms characterized by ineffective hematopoiesis, progressive cytopenias, and risk of progression to acute myeloid leukemia [1,2]. MDS experience anemia [3] which can lead to symptoms of fatigue, cardiac morbidity, and negative impacts on health-related quality of life (HRQoL) [4,5,6,7,8,9]. Treatment with RBC transfusions can provide transient relief in anemia-related symptoms, fatigue and dyspnea, which can be associated with short-term improvements in HRQoL measures such as physical, role, and social functioning [11,12]. Long-term dependence on RBC transfusions, is associated with poor prognosis and can cause complications due to iron overload including hepatic and cardiac organ failure; these conditions can further exacerbate negative impacts on patients’ HRQoL [13,14,15,16,17]

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