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Radiographically assessed body composition (BC) variables, including muscle and adipose tissue, may serve as prognostic biomarkers in patients with metastatic renal cell carcinoma (mRCC). We examined associations between baseline BC variables and outcomes for 99 patients with mRCC receiving first-line ipilimumab/nivolumab. Low skeletal muscle index (SMI) and low subcutaneous adipose tissue index (SATI) were associated with significantly better progression-free survival. Introduction: Biomarkers are needed to identify patients with metastatic renal cell carcinoma (mRCC) most likely to benefit from immune checkpoint inhibitors. We examined associations between radiographically assessed body composition (BC) variables and body mass index (BMI) with clinical outcomes for patients with mRCC receiving first-line ipilimumab + nivolumab (ipi/nivo). Patients and Methods: We retrospectively reviewed all patients with mRCC treated with first-line ipi/nivo at one institution before June 1, 2021 with an analyzable baseline computed tomography (CT) scan. BC variables (skeletal muscle index [SMI], subcutaneous adipose tissue index [SATI], and visceral adipose tissue index [VATI]) were measured using baseline CT scans. Relationships between BC variables and clinical outcomes were examined using Cox proportional hazard regression models. Results: Ninety-nine patients were analyzed (74% male, 64% overweight/obese, 75% low SMI). Controlling for age, IMDC risk, and sex (for BMI analyses), high vs. low SMI (HR = 2.433, CI: 1.397-4.238, P = .0017), high vs. low SATI (HR = 1.641, CI: 1.023-2.632, P = .0398), and obese BMI (≥ 30 kg/m²) vs. normal/overweight BMI (< 30 kg/m²) (HR = 1.859, CI: 1.156-2.989, P = .0105) were significantly associated with progression-free survival (PFS). Median overall survival (OS) for low SMI patients was higher (42.74 months, CI: 26.84, NR) than median OS for high SMI patients (27.01 months, CI: 15.28, NR) (adjusted HR = 1.728, CI: 0.909-3.285, P = .0952). No BC variables were significantly associated with OS or objective response rate. Conclusions: Low SMI and low SATI were associated with significantly better PFS for patients with mRCC receiving first-line ipi/nivo. Radiographic BC variables may be useful prognostic biomarkers in this setting. [ABSTRACT FROM AUTHOR]