Influence of body composition on the efficacy of nivolumab plus ipilimumab for metastatic clear cell renal cell carcinoma.

Increasing Skeletal Muscle Mass Index (SMMi) was independently associated with shorter progression-free survival in metastatic ccRCC patients treated with first-line nivolumab+ipilimumab.

• HR 1.50, 95% CI 1.05 to 2.15 per 3-unit increase in SMMi
• Association was evaluated using multivariable Cox regression models guided by directed acyclic graphs with non-linear cubic splines
• Analysis included 309 patients (80.3% male, median age 61.9 years)
• Body composition was measured using an AI segmentation tool at the L3 vertebra from pretreatment CT scans obtained within 45 days prior to starting therapy

Increasing Subcutaneous Adipose Tissue Index (SATi) was independently associated with shorter progression-free survival in metastatic ccRCC patients treated with first-line nivolumab+ipilimumab.

• HR 1.39, 95% CI 1.01 to 1.90 per 10-unit increase in SATi
• Association was independent of SMMi and other covariates in multivariable models
• Patient cohort included 61.8% intermediate-risk and 28.5% poor-risk patients by IMDC criteria
• Patients were treated at MD Anderson Cancer Center between June 2015 and February 2024

The associations of BMI, visceral adiposity, and skeletal muscle density with progression-free survival were inconclusive.

• BMI, visceral adipose tissue measures, and skeletal muscle density did not show statistically significant independent associations with PFS
• This finding suggests BMI is an imprecise surrogate for underlying adipose and muscle compartments
• All body composition measures also showed indeterminate associations with overall survival (OS)

Overall survival associations for all body composition measures were indeterminate.

• Neither SMMi, SATi, BMI, visceral adiposity, nor skeletal muscle density showed conclusive associations with OS
• Endpoints evaluated included both real-world progression-free survival (PFS) and overall survival (OS)
• The cohort of 309 patients was retrospectively analyzed

In an exploratory single-cell RNA sequencing analysis, low SMMi was associated with numerically higher T-cell fractions, fewer myeloid cell proportions, and higher IDO1 expression.

• Analysis used single-cell RNA sequencing from 12 treatment-naïve patients with metastatic ccRCC stratified by median SMMi and SATi values
• Higher T-cell fractions in low SMMi group: p=0.064
• Fewer myeloid cell proportions in low SMMi group: p=0.10
• Higher IDO1 expression was observed in the low SMMi group
• These findings were described as exploratory and did not reach conventional statistical significance thresholds

The study retrospectively analyzed 309 patients with metastatic clear cell RCC treated with first-line nivolumab+ipilimumab at a single institution.

• 80.3% of patients were male with a median age of 61.9 years
• 61.8% were intermediate-risk and 28.5% were poor-risk by IMDC criteria
• Treatment occurred between June 2015 and February 2024 at MD Anderson Cancer Center
• Body composition was measured using an artificial intelligence segmentation tool at the L3 vertebra from pretreatment CT scans obtained within 45 days prior to starting therapy