How to use luspatercept and erythropoiesis-stimulating agents in low-risk myelodysplastic syndrome

Abstract

Anaemia is the most common cytopenia in myelodysplastic syndrome (MDS), significantly impacting quality of life and morbidity. Erythropoiesis-stimulating agents (ESAs) are the first-line treatment for anaemia in lower risk (LR)-MDS. The European Medicines Agency (EMA) approved epoetin alpha for LR-MDS-related anaemia in 2017, based on evidence from a unique randomized Phase 3 trial and accumulated evidence in many trials, providing support to an already widely utilized therapeutic option. Luspatercept, a more recently approved agent, is a ligand trap for transforming growth factor beta (TGF-β) pathway, whose activation is associated with impaired terminal erythroid maturation in MDS. Luspatercept facilitates late-stage erythroid differentiation, improving transfusion-dependent anaemia in LR-MDS, and has shown activity after ESA failure in MDS-ring sideroblasts (RS) and in all subtypes of MDS ESA naïve transfusion-dependent patients. Due to the recent approval of luspatercept also in ESA naïve LR-MDS, it has become crucial to determine the optimal treatment algorithm for anaemic LR-MDS, before and after transfusion dependence. ESAs and luspatercept are characterized by distinct mechanisms of action, and their integration into treatment strategies is already possible, but requires further evidence to maximize efficacy and improve patient outcomes.

Keywords: ESAs; anaemia; erythropoietin; low‐risk myelodysplastic syndromes; luspatercept; transfusion dependence.