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Associations between body composition features and clinical outcomes in metastatic clear cell renal cell carcinoma patients treated with immune checkpoint blockade.

Purpose High body mass index (BMI) may lead to improved immune-checkpoint blockade (ICB) outcomes in metastatic clear cell renal cell carcinoma (mccRCC). However, BMI is a crude body size measure. We investigated BMI and radiographically assessed body composition (BC) parameters association with mccRCC ICB outcomes. Patients and methods Retrospective study of ICB treated mccRCC patients. BMI and BC variables (skeletal muscle index (SMI), and multiple adiposity indexes) were determined using pre-treatment CT scans. We examined the associations between BMI and BC variables with ICB outcomes. Therapeutic responses per RECIST V1.1 were determined. We compared whole transcriptomic patterns with BC variables in a separate cohort of 62 primary tumor samples. Results 205 mccRCC patients included in the cohort (74% were male, 71% were overweight/obese, and 53% were classified as low SMI). High BMI patients experienced longer overall survival (OS) than normal weight patients (unadjusted HR 0.66 (95% CI: 0.45-0.97); p=0.035). The only BC variable associated with OS was SMI (unadjusted HR comparing low vs. high SMI 1.65 (95% CI: 1.13-2.43); p=0.009). However, this OS association became non-significant after adjusting for IMDC score and line of therapy. No OS association was seen for adiposity and no BC variable was associated with progression-free survival or radiological responses. Tumors from patients with low SMI displayed increased angiogenic, inflammatory, and myeloid signals. Conclusion Our findings highlight the relevance of skeletal muscle in the BMI paradox. Future studies should investigate if addressing low skeletal muscle in metastatic patients treated with ICB can improve survival.