Body mass index–stratified outcomes with first-line immunotherapy in metastatic RCC: A real-world analysis.

Abstract

e16507 Background: Obesity is a known risk factor for renal cell carcinoma (RCC) yet paradoxically has been linked to better survival once the disease develops. This “obesity paradox” has been described in patients receiving immune checkpoint inhibitors (ICIs), though data in RCC remain limited. Methods: We conducted a retrospective cohort study using TriNetX, including patients diagnosed after January 2015. Inclusion criteria were adult patients with metastatic RCC, a recorded baseline body mass index (BMI) within six months of diagnosis, and receipt of first-line ICI therapy (nivolumab, ipilimumab, or pembrolizumab) within six months of diagnosis. Patients were stratified into two groups based on BMI (≥25 kg/m² vs 18.5– < 25 kg/m²). To reduce confounding, 1:1 propensity score matching was performed using demographic characteristics, comorbidities, and baseline hemoglobin, LDH, and albumin. Outcomes included all-cause mortality and healthcare utilization (emergency department [ED] visits, hospitalizations, and ICU admissions). In subgroup analyses, the BMI ≥25 kg/m² cohort was further stratified into overweight (25–29.9 kg/m²) and obese (≥30 kg/m²) groups. Effect estimates are reported as hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 64,160 patients with metastatic RCC, 2,471 met inclusion criteria in the BMI ≥25 kg/m² group and 1,623 in the BMI 18.5– < 25 kg/m² group. After matching, 1,390 patients were included in each cohort. Median follow-up was 12 months in both groups; mean age at ICI initiation was 65 years, and 73% were male. Patients with BMI ≥25 kg/m² had lower 1-year all-cause mortality compared with those with BMI 18.5– < 25 kg/m² (31% vs. 35%; HR 0.86, 95% CI 0.75–0.99). At 3 years, mortality remained numerically lower in the higher-BMI group (50% vs. 53%), although this difference did not reach statistical significance (HR 0.90, 95% CI 0.80–1.01). Rates of emergency department visits, hospitalizations, and ICU admissions were similar between groups at both 1 and 3 years. In subgroup analyses among patients with BMI ≥25 kg/m², those with obesity (BMI ≥30 kg/m²) had lower all-cause mortality than overweight patients (BMI 25–29.9 kg/m²), with reduced 1-year mortality (27% vs. 32%; HR 0.82, 95% CI 0.70–0.96) and reduced 3-year mortality (HR 0.87, 95% CI 0.76–0.97). Healthcare utilization outcomes were comparable between these subgroups. Conclusions: In this matched real-world cohort of ICIs-treated metastatic RCC, higher BMI was associated with lower 1-year mortality, though this effect was not maintained at 3 years. Among patients with BMI ≥25 kg/m², obesity was associated with better survival than overweight status. Healthcare utilization was similar across BMI groups. These findings are hypothesis-generating and suggest that body composition and metabolic–inflammatory factors may influence outcomes. Future studies should address these factors.