Novel agents and evolving strategies for anemia management in lower-risk myelodysplastic syndromes.

Abstract

Recent developments in the treatment of lower-risk myelodysplastic syndromes have focused on improving anemia management, which remains a major clinical challenge. Erythropoiesis-stimulating agents (ESAs) and lenalidomide are the standard therapies; however, their effectiveness is limited by resistance and patient selection criteria. Luspatercept, a transforming growth factor-beta superfamily ligand trap, has shown improved transfusion independence and is now considered a frontline option for a broader group of patients. Clinical trials have indicated that luspatercept provides a sustained response in several cases. Imetelstat, a telomerase inhibitor, offers an alternative for patients who do not respond to ESAs and has been shown to reduce the clonal mutation burden, suggesting possible disease-modifying effects. However, unresolved issues remain, such as the lack of predictive biomarkers to guide therapy selection, uncertainty about the optimal sequencing or combination of available treatments, and the fact that most patients eventually progress to higher-risk disease. Additionally, the real-world use of these new agents remains limited in some regions owing to issues with local introduction and reimbursement. This review summarizes recent clinical data on luspatercept and imetelstat, highlights their current limitations, and discusses areas for future research based on recent trial outcomes and evolving clinical practices.