Therapeutic approaches for the management of higher risk myelodysplastic syndromes

The heterogeneous nature of myelodysplastic syndromes (MDS) demands a risk-adapted therapeutic approach, and higher risk MDS, characterized by an increased risk of transformation into acute myeloid leukemia and inferior survival, is typically defined based on an integrated assessment of cytopenias, bone marrow blast percentage, and cytogenetic findings using the revised International Prognostic Scoring System. Incorporating mutational data could further refine the risk assessment and identify those with higher-than-expected disease risk. The principal therapeutic goal in this disease subset is to modify the natural history and prolong survival. Allogeneic stem cell transplant, the only potentially curative treatment, should be offered to eligible patients. Hypomethylating agents are the only approved treatment with unsatisfactory response rates and duration, and patients who failed prior hypomethylating agents unfortunately have dismal outcomes with urgent need of novel therapeutic agents. In this review, we provide the therapeutic landscape in higher risk MDS based on the current evidence and discuss the investigational treatment options under development.