The predictive efficacy of tumor mutation burden in immunotherapy across multiple cancer types: A meta-analysis and bioinformatics analysis

Purpose: To explore the predictive efficacy of tumor mutation burden (TMB) as a potential biomarker for cancer patients treated with Immune checkpoint inhibitors (ICIs). Methods: We systematically searched PubMed, Cochrane Library, Embase and Web of Science for clinical studies (published between Jan 1, 2014 and Aug 30, 2021) comparing immunotherapy patients with high TMB to patients with low TMB. Our main endpoints were objective response rate (ORR), durable clinical benefit (DCB), overall survival (OS) and progress-free Survival (PFS). Moreover, we downloaded simple nucleotide variation (SNV) data of 33 major cancer types from the TCGA database as non-ICIs group, and compared the high TMB patients' OS between the non-ICIs group and meta-analysis results. Results: Of 10,450 identified studies, 41 were eligible and were included in our analysis (7713 participants). Compared with low TMB patients receiving ICIs, high TMB yielded a better ORR (RR = 2.73; 95% CI: 2.31-3.22; P = 0.043) and DCB (RR = 1.93; 95% CI: 1.64-2.28; P = 0.356), and a significantly increased OS (HR =0.24; 95% CI: 0.21-0.28; P < 0.001) and PFS (HR = 0.38; 95% CI: 0.34-0.42; P < 0.001). Furthermore, compared with non-ICIs group from the TCGA database, immunotherapy can improve OS in some cancer types with high TMB and better prognosis, including colorectal cancer, gastric cancer, lung cancer, melanoma and pan-cancer. Conclusion: TMB is a promising therapeutic and prognostic biomarker for immunotherapy, which indicates a better ORR, DCB, OS and PFS. If there is a standard for TMB assessment and cut-off, it could improve the management of different cancers.