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Tumor Mutational Burden and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

 Jong Yeob Kim  ;  Andreas Kronbichler  ;  Michael Eisenhut  ;  Sung Hwi Hong  ;  Hans J. van der Vliet  ;  Jeonghyun Kang  ;  Jae Il Shin  ;  Gabriele Gamerith 
 CANCERS, Vol.11(11) : E1798, 2019 
Journal Title
Issue Date
CTLA-4 inhibitor ; PD-1 inhibitor ; PD-L1 inhibitor ; hazard ratio ; immune checkpoint inhibitors ; overall survival ; progression-free survival ; tumor mutational burden
Tumor mutational burden (TMB) is a genomic biomarker that predicts favorable responses to immune checkpoint inhibitors (ICIs). Here, we set out to assess the predictive value of TMB on long-term survival outcomes in patients undergoing ICIs. We systematically searched PubMed, Embase, CENTRAL and clinicaltrials.gov from inception to 6 August 2019. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival (OS) and/or progression-free survival (PFS) according to TMB. Data on 5712 patients from 26 studies were included. Among patients who received ICIs, high TMB groups showed better OS (HR 0.53, 95% CI 0.42 to 0.67) and PFS (HR 0.52, 95% CI 0.40 to 0.67) compared to low TMB groups. In patients with high TMB, those who received ICIs had a better OS (HR 0.69, 95% CI 0.50 to 0.95) and PFS (HR = 0.66, 95% CI = 0.47 to 0.92) compared to those who received chemotherapy alone, while in patients with low TMB, such ICI benefits of OS or PFS were not statistically significant. In conclusion, TMB may be an effective biomarker to predict survival in patients undergoing ICI treatment. The role of TMB in identifying patient groups who may benefit from ICIs should be determined in future randomized controlled trials.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Jeonghyun(강정현) ORCID logo https://orcid.org/0000-0001-7311-6053
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
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