Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/-25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p=0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR=1.66 [95% CI: 1.05-2.61]; p=0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR=2.19 [95% CI: 1.31-3.64]; p=0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR=2.19 [1.31-3.67]; p=0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.