Baseline and longitudinal body composition profile association with immune-checkpoint inhibitor (ICI) outcomes in metastatic clear-cell renal cell carcinoma (mccRCC).

553 Background: Body composition parameters, including skeletal muscle and fat distribution, have been associated with outcomes in mccRCC. However, limited data exist on dynamic body composition changes during ICI therapy and their relationship to treatment outcomes. Methods: We retrospectively analyzed 287 patients with mccRCC treated with ICI +/- tyrosine kinase inhibitors (TKIs) at Johns Hopkins University (2012–2023). Eligible patients received ≥4 weeks of ICI and had baseline CT imaging. Automated body composition metrics were extracted from CT scans at baseline and 3 months using the Data Analysis Facilitation Suite (DAFS). Quantified indices included body mass index (BMI), skeletal muscle index (SMI), subcutaneous (SATI), visceral (VATI), and intramuscular adipose tissue index (IMATI). Obesity was defined as BMI ≥25 kg/m². High vs. low VATI and SATI were categorized by sex-specific medians; sarcopenia (low SMI) was defined as SMI <35 cm²/m² in females or <55 cm²/m² in males. An optimized IMATI cutoff of 7.0 was applied, as no validated standard exists. Overall survival (OS) and progression-free survival (PFS) from the start of ICI were assessed using Kaplan-Meier and Cox regression models. Results: A total of 155 patients met inclusion criteria; 75% were male, median age was 63 years, and 82% were White. 97 patients (63%) received ICI monotherapy or dual ICI, and 58 (37%) received ICI + TKI. On multivariable analysis, higher baseline IMATI (>7.0) was independently associated with worse OS (HR 1.95, 95% CI 1.05–3.60, p=0.03). In the 3-month landmark analysis, an increase in VATI correlated with improved OS (HR 0.78 per SD, 95% CI 0.62–0.98, p=0.04), while an increase in IMATI showed a favorable trend (HR 0.82 per SD, 95% CI 0.66–1.02, p=0.07). When evaluating the 3-month IMATI value (cutoff >7.0) in a univariate model, higher IMATI remained directionally associated with worse OS (HR 1.76, 95 % CI 0.92–3.34, p = 0.09) but did not reach statistical significance. No significant differences were observed for PFS. Other parameters, including BMI, SMI, and SATI, were not significantly associated with survival or radiologic response. Conclusions: An optimized IMATI cutoff of 7.0, for which no validated standard currently exists, identified patients with poorer survival when above this threshold. Baseline IMATI was independently associated with inferior OS, and higher IMATI at 3 months remained directionally adverse but nonsignificant. Although early increases in VATI and IMATI correlated with improved OS, these effects attenuated after adjustment, likely reflecting selection among patients who remained on therapy. These findings suggest that baseline body composition, particularly intramuscular adiposity may carry stronger prognostic value than short-term compositional changes during ICI therapy in mccRCC.