Body mass index and mortality in immune checkpoint inhibitor–treated cancers: A real-world propensity-matched analysis.

11069 Background: Immune checkpoint inhibitors (ICIs) are a cornerstone of treatment for multiple solid tumors, including lung cancer and melanoma. Emerging evidence suggests that body mass index (BMI) may influence outcomes with immunotherapy, though findings remain inconsistent and largely derived from clinical trial populations. We evaluated the association between BMI and mortality among patients with cancers treated with ICIs using real-world data. Methods: We conducted a retrospective observational study using data from TriNetX, a global real-world research platform based on de-identified electronic health records. Adult patients with lung cancer or melanoma who received immune checkpoint inhibitor therapy, including durvalumab, pembrolizumab, nivolumab, ipilimumab, or atezolizumab, were identified. Patients were stratified by documented baseline body mass index into two groups: BMI 19–24.9 (Normal) and BMI 30–49.9 (Obese). To address baseline differences, 1:1 propensity score matching (PSM) was performed using demographics and major comorbidities. The primary endpoint was all-cause mortality; secondary endpoints included inpatient hospitalization frequency. Results: Before matching, the cohorts consisted of 7,951 patients (BMI 30–49.9) and 4,651 patients (BMI 19–24.9). After PSM, 4,152 patients were included in each cohort. Baseline characteristics, including age (mean 67 years), sex (59% male), and comorbidities (hypertension, diabetes, CKD), were well-balanced (p > 0.05).All-cause mortality was significantly higher in the BMI 19–24.9 group compared to the BMI 30–49.9 group (49.2% vs 43.4%), with a risk ratio of 0.88 (95% CI,0.84–0.92; p < 0.001). Overall survival was significantly longer in the obese cohort, with a median survival of 1,043 days compared to 579 days in the normal BMI cohort. High BMI was associated with a 27.5% reduction in the hazard of death (HR 0.725, 95% CI 0.68–0.77; p < 0.001). Conversely, the high BMI cohort had a higher risk of inpatient encounters (57.6% vs 55.3%; p = 0.032) and a higher mean number of hospitalizations (5.4 vs 4.6; p < 0.001). Conclusions: In this large real-world study, higher BMI was associated with significantly lower mortality and nearly double the median survival time in patients treated with ICIs. While higher BMI was also associated with increased hospitalization frequency, the overall survival benefit remains robust. These findings support the "obesity paradox" in immunotherapy and suggest that nutritional status is a critical determinant of long-term ICI efficacy and healthcare utilization.