Association between body mass index and overall survival in veterans receiving immune checkpoint inhibitors.

11149 Background: While obesity is a well-established risk factor for cancer development, patients with obesity paradoxically demonstrate better survival rates compared to those with normal body mass index (BMI) in certain malignancies. Studies suggest this phenomenon extends to patients receiving immune checkpoint inhibitors (ICI), with emerging evidence showing improved progression-free and overall survival across multiple cancer types. Despite recognition of this relationship, its magnitude and consistency in real-world populations remain uncertain. The Veterans Affairs (VA) healthcare system, with its comprehensive electronic health records and distinctive demographic composition, presents a unique opportunity to validate these findings in routine clinical practice. Methods: We conducted a retrospective analysis using the VA Corporate Data Warehouse, selecting de-identified patients who received ICI therapy between March 2011 and June 2024 (VA COIN grant #1I50HX004009, IRB #1575166). From an initial cohort of 37,863 veterans, we chose a random 20% subset (n = 7,302) for preliminary analysis. We extracted demographic data (age, sex, race), vital signs for BMI calculation, cancer diagnoses (ICD-9/10 codes), and ICI records. BMI categories were: underweight (< 18.5 kg/m²), normal (18.5-25 kg/m²), overweight (25-30 kg/m²), and obesity (> 30 kg/m²). We calculated overall survival from ICI initiation to death or last follow-up. Survival analyses included Kaplan-Meier methodology with Cox proportional hazards models. Results: The cohort of 7,302 veterans was predominantly male (97%) and White (74%), with most patients aged 65-75 years (51%). Pembrolizumab (45%) and nivolumab (29%) were the most frequently prescribed ICIs. Survival was significantly associated with BMI class (log-rank test p < 0.01). Using normal BMI (18.5-25, n = 2,422) as reference, Cox proportional hazards analysis showed progressively lower mortality risk with increasing BMI, ranging from 13% reduction in overweight patients (HR 0.87, 95% CI 0.82-0.93) to 27% reduction in patients with BMI 35-40 (n = 481, HR 0.73, 95% CI 0.65-0.83, p < 0.01). Underweight patients showed increased mortality risk (HR 1.31, 95% CI 1.15-1.51). Conclusions: The 27% mortality reduction among patients with higher BMI demonstrates a clinically meaningful survival advantage in immunotherapy outcomes and suggests BMI might be an important factor in risk stratification and treatment discussions. The increased mortality risk in underweight patients may reflect cancer-related cachexia. These findings, derived from a large cohort of veterans, corroborate the obesity paradox in cancer immunotherapy and suggest potential applications for personalized immunotherapy approaches.