Impact of body composition on outcomes of immune checkpoint inhibitor combination therapy in patients with previously untreated advanced renal cell carcinoma

Data on the association between body composition and outcomes in patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitor (ICI) combination therapy are limited. We retrospectively evaluated the clinical and radiographic data of 159 patients with advanced RCC, including 84 receiving ICI dual combination therapy (immunotherapy [IO]-IO group) and 75 receiving combinations of ICIs with tyrosine kinase inhibitors (TKIs) (IO-TKI group). Pretreatment computed tomography images were used to calculate body composition, including skeletal muscle mass and fat tissue area. Sarcopenia was defined based on skeletal muscle and psoas muscle indexes. The total fat index, subcutaneous fat index (SFI), and visceral fat index were also calculated. In the IO-IO treatment group, there was no significant association between body composition and survival or tumor response ( P > 0.05). In the IO-TKI treatment group, the high SFI was associated with longer progression-free survival (hazard ratio, 2.70; P  = 0.0091) and overall survival (hazard ratio, 26.0; P  = 0.0246) than the low SFI, which remained significant after adjusting for covariates. Furthermore, in the high-SFI population, patients treated with IO-TKI therapy had longer progression-free survival ( P  = 0.0019) and overall survival ( P  = 0.0287) than those treated with IO-IO therapy, while there was no significant survival difference between the 2 treatment groups in the low-SFI population ( P > 0.05). The SFI can be potentially utilized as an effective predictive and prognostic biomarker for first-line ICI combination therapy for advanced RCC.