Impact of body mass index on immunotherapy outcomes and complications in solid tumor patients: A real-world evidence analysis.

2603 Background: Obesity alters immune function by modifying cytokine profiles and altering immune cells. Body mass index (BMI) influences cancer outcomes, including response to therapy. Several studies have shown that patients (pts) with a higher BMI respond better to immunotherapy (IT). This study assesses the impact of BMI on IT outcomes, admission risk, and major complications in pts with solid tumors. Methods: We utilized TriNetX, a global data platform from 104 healthcare institutions, to analyze outcomes in cancer pts on IT. Patients were categorized into two groups: BMI < 25 (n = 8,460) and BMI ≥ 25 (n = 13,631). Propensity Score Matching balanced groups for age, sex, race, comorbidities, smoking status, and alcohol use. Pts aged 18–65 years with solid tumors who received ≥1 IT dose were included with a 1-year follow-up. IT regimens included PD-L1, PD-1, or CTLA-4 antibodies. Cancers analyzed: esophagus, bladder, stomach, endometrium, melanoma, lung, kidney, head and neck, and breast. Outcomes included: ICU admissions, hospital admissions, mortality, heart failure, ischemic stroke/transient ischemic attack (TIA), venous thromboembolism (VTE), myocardial infarction, polyneuropathy, pneumonitis/pneumonia, and acute kidney injury (AKI). Risks were assessed using 1-year event-free survival and survival analysis. Results: After 1:1 PSM, the two groups each consisted of 8,460 pts, with balanced baseline variables. Post-matching, the mean age was ~52.5 ± 9 years, 56.0% were White, and 54.7% were female. A BMI < 25 was found to be a predictor of increased risk for multiple adverse outcomes. The 1-year risk-free survival was significantly lower in pts with BMI < 25 compared to those with BMI ≥ 25 for ischemic stroke/TIA (94.6% vs. 95.9%, log-rank P < 0.01), ICU admissions (83.3% vs. 89.05%, P < 0.01), hospital admissions (37.5% vs. 48.1%, P < 0.01), mortality (64.01% vs. 80.62%, P < 0.01), heart failure (84.3% vs. 87.6%, P < 0.01), and pneumonitis/pneumonia (79.1% vs. 84.9%, P < 0.01). However, there was no significant difference in the incidence of VTE, myocardial infarction, polyneuropathy, or AKI (P > 0.05). We performed several sensitivity analyses using different BMI cutoff groups and compared outcomes to the BMI < 25 group. In these balanced comparisons, we found similar trends except for an increased incidence of polyneuropathy in BMI ≥ 35 compared to BMI < 25 (1-year risk-free: 89.2% vs. 91.6%, P < 0.01) and in BMI ≥ 40 compared to BMI < 25 (1-year risk-free: 89.0% vs. 91.4%, P < 0.01). Conclusions: Our study provides real-world evidence on the types of complications experienced by pts with BMI < 25 when treated with IT for different types of solid tumors. It also explains, at least partly, the improved outcomes and tolerability observed in pts with higher BMI receiving IT. Based on our findings—such as the increased risk of hospital admissions and pneumonitis—we postulate that pts with low BMI may have a stronger inflammatory reaction to IT, leading to a higher incidence of complications.