Evaluating Real-World Outcomes in Treatments for Lower-Risk MDS

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Real-world evidence and patient-reported outcomes provide crucial validation for clinical treatment decisions in lower-risk myelodysplastic syndrome (MDS), particularly given that quality of life improvement is the principal management objective. A post hoc analysis of the COMMANDS trial presented at European Hematology Association 2024 explored the relationship between hemoglobin levels and health-related quality of life using validated measures including EORTC Core Quality of Life and Functional Assessment of Cancer Therapy-Anemia questionnaires. The study found that achieving hemoglobin levels of 10 g/dL or greater was associated with higher likelihood of quality of life improvement, providing evidence-based targets for treatment optimization.

These quality-of-life data directly influence clinical practice by reinforcing dose titration strategies for luspatercept. Beyond just transfusion requirements, maintaining hemoglobin above 10 g/dL becomes a therapeutic goal, guiding clinicians to escalate luspatercept doses appropriately when patients have received at least 2 doses but haven’t achieved this hemoglobin threshold. This approach emphasizes the multifaceted nature of treatment success, incorporating both transfusion independence and functional hemoglobin levels that correlate with improved patient-reported outcomes and daily functioning.

A retrospective real-world analysis presented at Society of Hematologic Oncology 2024 examined erythropoiesis-stimulating agent (ESA) utilization and outcomes in community-treated patients with lower-risk MDS, revealing concerning efficacy gaps. Using National Comprehensive Cancer Network guidelines’ definition of ESA failure (lack of 1.5 g/dL hemoglobin improvement and/or decreased transfusion requirements), only one-third of patients achieved ESA response, while two-thirds experienced primary failure. Additionally, 50% of patients who were transfusion-independent at ESA initiation became transfusion-dependent over time. These findings highlight significant unmet needs in lower-risk MDS management and emphasize the importance of alternative therapies like luspatercept for patients not achieving clinical benefit from ESAs.