Optimizing Anemia Management in Low-Risk MDS: From ESAs to Targeted Therapies

Management of anemia in low-risk myelodysplastic syndrome (MDS) has evolved with a clearer understanding of patient selection and therapeutic sequencing. Erythropoiesis-stimulating agents (ESAs) have historically been a cornerstone for patients with symptomatic anemia, particularly those with lower endogenous erythropoietin levels and limited transfusion needs. However, not all patients derive benefit, and careful assessment of response—typically through hemoglobin improvement and reduced transfusion burden—is critical to guide ongoing use. For patients who are unlikely to respond or who lose response to ESAs, newer agents have expanded treatment options. Luspatercept, a first-in-class erythroid maturation agent, targets ineffective late-stage erythropoiesis and demonstrated meaningful clinical benefit in the MEDALIST and COMMANDS trials, leading to FDA approval. Understanding when to transition from ESAs to therapies such as luspatercept or imetelstat is key to improving outcomes and reducing transfusion dependence in this population.