Case-Based Discussion: Treatment Choices for LR-MDS

Case-Based Discussion: Treatment Choices for LR-MDS

The case discussion highlights management complexities in lower-risk MDS. A 77-year-old man with worsening anemia (Hb, 7.6 g/dL), elevated EPO level (>200 mU/mL), and no transfusion history presented with significant fatigue affecting daily function. Initial considerations included excluding reversible causes such as nutritional deficiencies, iron status, and occult bleeding. While earlier intervention might have improved his quality of life, insurance restrictions often limit access to agents such as luspatercept until transfusion dependence is established. In practice, a transfusion is sometimes required first to qualify for approval, despite the clinical appropriateness of initiating therapy sooner. The panel emphasized that proactive management aligned with patient-reported symptoms could provide substantial quality-of-life benefits.

Molecular testing and comprehensive disease assessment are stressed as critical components of decision-making. While this patient fit a lower-risk profile by traditional scoring, the experts caution that molecular abnormalities may alter prognosis, with some patients demonstrating adverse mutational features warranting closer monitoring or more aggressive therapy. For certain individuals with immunologic markers, immunosuppressive therapy may also be considered. The discussion reinforces that treatment planning should go beyond categorical risk assignments and incorporate evolving genomic and clinical data to avoid undertreating higher-risk biology masquerading as low risk.

A second illustrative case of a 70-year-old woman with lower-risk MDS, demonstrates the need for individualized treatment after ESA failure. With persistent symptomatic anemia and preserved counts, luspatercept is considered the most appropriate next-line therapy, though hypomethylating agents or clinical trials could be options in select contexts. Experts highlight the importance of tailoring therapy to comorbidities, cytopenia profile, and patient goals—such as resuming community engagement. Ultimately, both cases underscore the tension between guideline-driven algorithms and patient-centered decision-making, with therapy choices influenced by insurance access, mutational data, treatment durability, and the patient’s functional needs.