Molecular Insights and Therapeutic Advances in Low-Risk Myelodysplastic Neoplasms: A Clinical Review

Myelodysplastic neoplasms (MDS) are characterized by remarkable heterogeneity in clinical manifestations, posing significant management challenges arising due to genetic plasticity. While the Revised International Prognostic Scoring System (IPSS-R) has traditionally stratified MDS into higher-risk (HR) and lower-risk (LR) categories, the recently developed Molecular International Prognostic Scoring System (IPSS-M) integrates molecular signatures and has further enhanced prognostic stratification. In LR-MDS, current therapeutic interventions remain non-curative and the goal of treatment is centered along three critical axes: reducing transfusion dependence, improving quality of life, and reducing the risk of progression to acute myeloid leukemia (AML). This review examines recent progress made in the therapeutic landscape of LR-MDS, with particular emphasis on the molecular basis of these novel agents that may have disease-modifying potential. We evaluate the clinical trials and targeted agents in the pipeline for treating LR-MDS, providing a comprehensive perspective where these treatment modalities are placed in the current standard of care and how these novel targets can shape future therapeutic innovations.