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. 2021 Jul 29:11:706652.
doi: 10.3389/fonc.2021.706652. eCollection 2021.

Prognostic Role of Tumor Mutational Burden in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Taobi Huang  1   2   3 , Xia Chen  1   2   3 , Huiyun Zhang  1   2   3 , Yuan Liang  1   2   3 , Longquan Li  1   2   3 , Hui Wei  1   2   3 , Weiming Sun  4 , Yuping Wang  2   3
Affiliations

Prognostic Role of Tumor Mutational Burden in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Taobi Huang et al. Front Oncol. .

Abstract

Purpose: Immunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs.

Methods: We systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software.

Results: Pooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53-0.71; P <0.01) and PFS (HR: 0.51, 95% CI: 0.44-0.60; P <0.01) for the high TMB group receiving ICIs as compared to the low TMB group. Particularly, results were found to be more significant in studies with larger sample sizes (≥30), Western patients, higher TMB cutoff values (≥20 mut/Mb), anti-PD-1 therapy, and when the sample source was tissue and tumor type was either melanoma, small cell lung cancer, or gastric cancer.

Conclusion: TMB is a promising independent prognostic biomarker for cancer patients receiving ICIs, which could provide a new potential therapeutic strategy for high TMB patients who have failed traditional therapy. Furthermore, consistency in the key aspects of TMB assessment is expected in the future.

Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42021229016.

Keywords: cutoff; immune checkpoint inhibitor; overall survival; progression-free survival; tumor mutational burden.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
The flow diagram of the study selection process.
Figure 2
Figure 2
The forest plot of OS in patients with high TMB compared to those with low TMB. OS, overall survival; TMB, tumor mutational burden.
Figure 3
Figure 3
The forest plot of PFS in patients with high TMB compared to those with low TMB. PFS, progression-free survival; TMB, tumor mutational burden.
Figure 4
Figure 4
The subgroup analysis in OS of patients with high TMB compared to those with low TMB. OS, overall survival; TMB, tumor mutational burden.
Figure 5
Figure 5
The subgroup analysis of PFS in patients with high TMB compared to those with low TMB. PFS, progression-free survival; TMB, tumor mutational burden.
See this image and copyright information in PMC

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