Luspatercept: From Bench to Bedside and Beyond in the Management of Ineffective Erythropoiesis

Abstract

Luspatercept is a novel erythroid maturation agent that has emerged as a significant advancement in the management of ineffective erythropoiesis. By targeting the transforming growth factor-β superfamily signaling pathway, Luspatercept enhances late-stage erythroid differentiation. This review provides an in-depth exploration of its mechanism of action, pharmacologic properties, and clinical efficacy across multiple hematologic disorders. We summarize trial outcomes in lower-risk myelodysplastic syndromes, transfusion-dependent β-thalassemia, and myelofibrosis, highlighting improvements in erythroid response and transfusion independence. The article also discusses adverse event profiles and future directions, including ongoing trials and potential expansion of indications. Luspatercept represents a promising targeted erythroid therapy with benefits across several hematologic diseases.