Evolving Approaches in the Management of MDS

In an Editor’s Special Episode of the HemOnc Pulse, Andrew Brunner, MD, assistant professor of medicine at Harvard Medical School and at the Center for Leukemia at Massachusetts General Hospital covers a detailed discussion on the evolving treatment landscape for myelodysplastic syndromes (MDS), with a focus on therapeutic sequencing, recently approved agents, and the integration of molecular targets into clinical decision-making.

The conversation begins with a review of the IMerge phase 3 study, which evaluated the efficacy of imetelstat in patients with lower-risk, transfusion-dependent MDS who were either ineligible for erythropoiesis-stimulating agents (ESAs) or had received prior therapies. Data are presented on transfusion independence rates among subgroups with prior exposure to ESAs, luspatercept, lenalidomide, and hypomethylating agents. The discussion highlights that imetelstat maintains clinical activity following most prior therapies but shows diminished responses in patients previously treated with hypomethylating agents. The implications for sequencing imetelstat earlier in the treatment course are explored.

In the latter half of the episode, the conversation shifts to future directions in MDS care, emphasizing the increasing role of precision medicine. The guest expert addresses the molecular heterogeneity of MDS and describes the emerging use of targeted therapies, including inhibitors for IDH1 and IDH2 mutations. The discussion also covers ongoing research in splicing factor mutations like SF3B1 and challenges in developing therapies for patients with TP53-mutated disease, who remain at high risk for progression and treatment resistance.

This episode provides clinicians with clinically relevant insights into optimizing therapy for lower-risk MDS, including treatment sequencing strategies and the application of molecular data to guide individualized patient care. As the therapeutic landscape continues to expand, evidence-based decision-making and ongoing research remain central to improving outcomes in this patient population.