Association of Frailty With Transfusions, Hospitalizations, and Survival in Patients With Myelodysplastic Syndrome Initiating Hypomethylating Agents

Introduction Prognostic scoring systems in MDS lack functional status measures. We sought to evaluate the influence of frailty on overall survival and care utilization in a national cohort. We conducted a retrospective study in the US Veterans Affairs Healthcare System of patients with MDS initiated on hypomethylating agents (HMAs) from 2004 to 2023. Frailty was measured using the Veterans Affairs‐Frailty Index (VA‐FI). Methods For primary analyses, we evaluated the association between severity of frailty and overall survival via Kaplan–Meier analysis, followed by Cox proportional hazard regression models. Multivariable Poisson regression was used to evaluate transfusion incidence and unplanned hospitalizations. We identified 2285 veterans with MDS who initiated HMA treatment. The median age was 73.2 years. In addition, 34.0%, 30.6%, and 35.4% of veterans were classified as non‐frail, mildly frail, and moderate‐to‐severely frail, respectively. Results Moderate‐to‐severely frail veterans had a 49% higher hazard of death (aHR, 1.49; 95% CI, 1.34–1.67), as well as a higher incidence of transfusions (aIRR, 1.61; 95% CI, 1.45–1.80) and hospitalizations (aIRR, 1.58; 95% CI, 1.51–1.64). Conclusion Increasing frailty was associated with higher rates of death, hospitalizations, and transfusions. Further research is needed to characterize how MDS‐related contributors to frailty and non‐oncologic aging‐related factors mediate the increased risk of inferior outcomes in this population. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission