Prognostic Impact of Sarcopenia on Clinical Outcomes in Malignancies Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Background: The effect of sarcopenia on the clinical outcomes of patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is unclear. The aim of this study was to evaluate the effect and survival of patients with malignancies and sarcopenia receiving ICIs.

Methods: We systematically searched related studies in PubMed, Embase, and Cochrane Library up to March 2021 according to the inclusion and exclusion criteria. Information pertaining to the hazard ratio (HR) corresponding to 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) as determined by univariate and multivariate analyses; the odds ratio (OR) corresponding to the 95% CI of the disease control rate (DCR) and objective response rate (ORR); and immune-related adverse events (irAEs) was collected and analyzed using the RevMan 5.4 software. Study heterogeneity and sensitivity were also assessed.

Results: A total of 19 studies were finalized that included 1763patients with lung, gastrointestinal, and head and neck cancers as well as those with melanoma, renal cell carcinoma, urothelial carcinoma, pancreatic cancer, and soft tissue sarcoma. According to univariate and multivariate analyses, patients with sarcopenia at pre-immunotherapy had poorer PFS and OS than those without. HRs and the corresponding 95% CI of PFS were 1.91(1.55-2.34, p <0.00001) and 1.46 (1.20-1.78, p =0.0001), respectively, and HRs and the corresponding 95% CI of OS were 1.78 (1.47-2.14, p <0.00001) and 1.73 (1.36-2.19, p <0.0001), respectively. Patients with sarcopenia showed poor PFS and OS during treatment. In addition, patients with sarcopenia had worse ORR (OR 0.46, 95% CI 0.28-0.74, p = 0.001) and DCR (OR 0.44, 95% CI 0.31-0.64, p<0.0001); however, the incidence of irAEs of any grade and high-grade in patients with sarcopenia did not increase, OR and the corresponding 95% CI were 0.58(0.30-1.12, p = 0.10) and 0.46(0.19-1.09, p = 0.08). Further, we performed subgroup analysis, skeletal muscle mass index (SMI) and psoas muscle mass index (PMI) stratification. In the SMI group, patients with sarcopenia had poor ORR, DCR, PFS, and OS than those without. In the PMI group, sarcopenia had poor ORR,DCR, and was a poor prognostic factor for PFS and OS according to univariate analysis but had no effect on PFS and OS according to multivariate analysis.

Conclusions: Patients with malignancies and sarcopenia at pre-immunotherapy or follow-up visits had poorer clinical outcomes than those without, and sarcopenia was a poor predictive factor of ICI immunotherapy outcomes.