PMID- 35355708 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220401 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - The Predictive Value of Tumor Mutation Burden on Clinical Efficacy of Immune Checkpoint Inhibitors in Melanoma: A Systematic Review and Meta-Analysis. PG - 748674 LID - 10.3389/fphar.2022.748674 [doi] LID - 748674 AB - Background: Tumor mutational burden (TMB) is a genomic biomarker that can predict favorable responses to immune checkpoint inhibitors (ICIs). Although we have better understanding of TMB in cancer immunity and cancer immunotherapy, the relationship between TMB and the clinical efficacy of ICIs remains unknown in the treatment of melanoma patients. Here, we conduct a systematic review and meta-analysis to evaluate the predictive value of TMB on the efficacy of ICIs in patients with melanoma. Methods: We systematically collected data from PubMed, Embase, Cochrane Library, CNKI, China Biomedical Database (CBM), and Wanfang Database. The end date was set to 26 June 2021. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival and/or progression-free survival according to TMB. Data for 1,493 patients from 15 studies were included. In addition, pooled effect size, heterogeneity analysis, sensitivity analysis, publication bias detection, and subgroup analysis were performed based on the included data. Results: Patients with high TMB showed significantly improved OS (HR = 0.49, 95% CI: 0.33, 0.73; p = 0.001) and PFS (HR = 0.47, 95% CI: 0.33, 0.68; p < 0.001) compared with patients with low TMB. This association was very good in patients treated with monotherapy, that is, anti-CTLA-4 or anti-PD-(L)-1 inhibitors, but not for the patients treated with a combination of the two drugs. The subgroup analysis results showed that heterogeneity was substantial in the targeted next-generation sequencing (NGS) group. Publication bias was detected, and the results were visualized using the funnel chart. And sensitivity analysis and trim-and-fill method analysis showed that our results were stable and reliable. Conclusion: High TMB is associated with improved OS and PFS in melanoma patients treated with mono-drug ICIs. TMB determined by NGS should be standardized to eliminate heterogeneity. Therefore, the role of TMB in identifying melanoma patients who may benefit from ICI should be further determined in more randomized controlled trials in the future. CI - Copyright (c) 2022 Ning, Liu, Wang, Li, Xu and Wei. FAU - Ning, Biao AU - Ning B AD - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Liu, Yixin AU - Liu Y AD - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Wang, Miao AU - Wang M AD - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Li, Yi AU - Li Y AD - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Xu, Tianzi AU - Xu T AD - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Wei, Yongchang AU - Wei Y AD - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital of Wuhan University, Wuhan, China. AD - Hubei Cancer Clinical Study Center Zhongnan Hospital of Wuhan University, Wuhan, China. LA - eng PT - Journal Article PT - Review DEP - 20220309 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8959431 OTO - NOTNLM OT - OS OT - PFS OT - immune checkpoint inhibitor OT - melanoma OT - meta-analysis OT - tumor mutation burden COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/04/01 06:00 MHDA- 2022/04/01 06:01 PMCR- 2022/03/09 CRDT- 2022/03/31 05:20 PHST- 2021/07/28 00:00 [received] PHST- 2022/02/10 00:00 [accepted] PHST- 2022/03/31 05:20 [entrez] PHST- 2022/04/01 06:00 [pubmed] PHST- 2022/04/01 06:01 [medline] PHST- 2022/03/09 00:00 [pmc-release] AID - 748674 [pii] AID - 10.3389/fphar.2022.748674 [doi] PST - epublish SO - Front Pharmacol. 2022 Mar 9;13:748674. doi: 10.3389/fphar.2022.748674. eCollection 2022.