The influence of body composition on the survival of patients with metastatic clear cell renal carcinoma (mccRCC) treated with nivolumab (nivo) + ipilimumab (ipi).

545 Background: Over the last decade, immune checkpoint therapy (ICT) has become the cornerstone of first-line treatment for mccRCC. Despite the widespread use, there is heterogeneity in tumor response to ICT, and there is growing interest in how host factors modulate the tumor microenvironment. Recent studies in patients with mccRCC and other malignancies suggest that ICT may be more effective in patients with higher body mass index (BMI). Since BMI is an imperfect surrogate for distinct compartments of adipose tissue and muscle, we investigated the influence of body composition on outcomes with first-line (1L) nivo + ipi in patients with mccRCC. Methods: A retrospective analysis was conducted on patients with mccRCC at MD Anderson Cancer Center from June 2015 to Dec 2021 who received nivo + ipi as 1L treatment for advanced or mccRCC. Clinical data including demographics, BMI, and IMDC risk score were collected. Body composition was measured using an AI segmentation tool at the L3 vertebra from a pre-treatment CT scan obtained within 45 days of starting nivo + ipi. Efficacy endpoints of interest were time to treatment discontinuation (TTD), progression-free survival (PFS) and overall survival (OS). We constructed flexible multivariable Cox regression models guided by directed acyclic graphs to flexibly model the association of treatment outcomes with body composition measures as continuous variable, including nonlinear terms as cubic splines, and adjusting for IMDC risk and sarcomatoid dedifferentation as confounders. Results: 209 patients received 1L nivo + ipi (78.5% male, median age of 61 years, 59.3% and 32.5% IMDC intermediate- and poor-risk). Increasing skeletal muscle mass (SMMi) was associated with inferior PFS (HR 1.52, 95% CI 1.01 - 2.31 for 1-unit increase), whereas BMI and adiposity measures were not associated with PFS. Body composition measures were not significantly associated with OS, yet noteworthy trends were observed for visceral adiposity (VATi, HR 0.69, 95% CI 0.42 - 1.15 for 1-unit increase) and SMMi (HR 1.22, 95% CI 0.72 - 2.07). Conclusions: In a large cohort of patients with mccRCC, skeletal muscle mass was surprisingly associated with inferior PFS on 1L nivo + ipi. These results build upon conflicting body composition studies in mccRCC and suggest that future studies should investigate how skeletal muscle influences the tumor microenvironment.