Association Between Blood-based Tumor Mutation Burden And Efficacy Of Immune Checkpoint Inhibitors:A Meta-analysis

Background:Immune checkpoint inhibitors(ICIs)have improved the survival outcomes in aspects of cancer patients.Effective and less invasive biomarkers are still necessary to identify the benefit patients.Several studies reported that blood tumor mutation burden(b TMB)may be a potential alternative biomarker to predict efficacy of ICIs.Objectives:In this study,Meta-analysis was used to evaluate the relationship between b TMB and the efficacy of immune checkpoint inhibitors,so as to clarify the role and clinical value of b TMB in the efficacy prediction of immune checkpoint inhibitors.Methods:We systematically searched Pub Med,Embase,and Cochrane databases form inception to 15 July 2020.The eligible studies should evaluate the association between b TMB and outcomes of ICIs.The extractions included hazard ratio(HR)and95% confidence interval(CI)of overall survival(OS)and progression-free survival(PFS)of each group.Pooled hazard ratio(HR)of progression-free survival(PFS)and overall survival(OS)were estimated by Stata version 15.0.We also conducted the heterogeneity analysis,sensitivity analysis,publication bias.Results:11 studies with 2,512 patients were finally included in the meta-analysis.In patients receiving ICIs,high b TMB group(b TMB-H)had better PFS(pooled HR0.53,95% CI 0.36-0.78,P = 0.001)),and OS(pooled HR 0.57,95% CI 0.36-0.92,P =0.021)compared to low b TMB group(b TMB-L).In patients with high b TMB,ICIs arm had a better PFS(pooled HR 0.64,95% CI 0.52-0.78,P < 0.001)and OS(pooled HR 0.64,95% CI 0.55-0.75,P < 0.001)compared to chemotherapy arm,while in patients with low b TMB,PFS and OS of ICIs arm were not significant difference with chemotherapy arm.Conclusion:b TMB may be able to predict the efficacy with ICIs and identify the patients who benefit from ICIs.The role of b TMB should be confirmed in future perspective large clinical trials of patients with ICIs treatment.