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Luspatercept in low-risk myelodysplastic syndromes: a paradigm shift in treatment strategies

Journal Title: 
Expert Opinion on Biological Therapy
Primary Author: 
Molica M
Author(s): 
Molica M, Rossi M
Original Publication Date: 
Saturday, March 30, 2024
Bone Marrow Disease(s): 

Introduction: In patients with myelodysplastic syndromes (MDS), anemia is prevalent affecting 80%-85% of low-risk (LR-MDS) patients, with 40% eventually requiring red blood cell (RBC) transfusions. Except forlenalidomide, exclusively approved for those with deletion of chromosome 5q,erythropoiesis-stimulating agents (ESAs) are the primary treatment choice for low-risk patients. Those unresponsive to ESAs face limited alternatives, eventually necessitating long-term RBC transfusions, leading to secondary iron overload and adversely affecting quality of life (QoL).

Area covered: Luspatercept is a pioneering erythroid maturation agent. It received approval by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for treating adults experiencing transfusion-dependent anemia associated with LR-MDS or β-thalassemia. Recently, the FDA approved luspatercept as first- line therapy in patients with very low- to intermediate-risk MDS who require RBC transfusions and have not previously received ESAs. This review summarizes the historical impact of luspatercept intreating LR-MDS unresponsive to ESAs and illustrates its potential benefit asfrontline therapy in MDS and its employment in patients with myelofibrosis-induced anemia.

Expert opinion: Luspatercept has revolutionized the therapeutic paradigm of LR-MDS, for which there was a limited therapeutic arsenal, especially in the setting of patients who did not respond or fail after ESA treatment.

Keywords: Low-risk myelodysplastic syndromes; erythtopoiesis stimulating agents; frontline therapy; luspatercept; red blood cells transfusions.