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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number1798
JournalCancers
Volume11
Issue number11
DOIs
Publication statusPublished - 2019 Nov

Fingerprint

Tumor Burden
Meta-Analysis
Disease-Free Survival
Survival
Biomarkers
PubMed
Randomized Controlled Trials
Retrospective Studies
Clinical Trials
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, J. Y., Kronbichler, A., Eisenhut, M., Hong, S. H., van der Vliet, H. J., Kang, J., ... Gamerith, G. (2019). Tumor mutational burden and efficacy of immune checkpoint inhibitors: A systematic review and meta-analysis. Cancers, 11(11), [1798]. https://doi.org/10.3390/cancers11111798
Kim, Jong Yeob ; Kronbichler, Andreas ; Eisenhut, Michael ; Hong, Sung Hwi ; van der Vliet, Hans J. ; Kang, Jeonghyun ; Shin, Jae Il ; Gamerith, Gabriele. / Tumor mutational burden and efficacy of immune checkpoint inhibitors : A systematic review and meta-analysis. In: Cancers. 2019 ; Vol. 11, No. 11.
@article{33a0373b5ff64ada972968107cdabee3,
title = "Tumor mutational burden and efficacy of immune checkpoint inhibitors: A systematic review and meta-analysis",
abstract = "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.",
author = "Kim, {Jong Yeob} and Andreas Kronbichler and Michael Eisenhut and Hong, {Sung Hwi} and {van der Vliet}, {Hans J.} and Jeonghyun Kang and Shin, {Jae Il} and Gabriele Gamerith",
year = "2019",
month = "11",
doi = "10.3390/cancers11111798",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "11",

}

Kim, JY, Kronbichler, A, Eisenhut, M, Hong, SH, van der Vliet, HJ, Kang, J, Shin, JI & Gamerith, G 2019, 'Tumor mutational burden and efficacy of immune checkpoint inhibitors: A systematic review and meta-analysis', Cancers, vol. 11, no. 11, 1798. https://doi.org/10.3390/cancers11111798

Tumor mutational burden and efficacy of immune checkpoint inhibitors : A systematic review and meta-analysis. / Kim, Jong Yeob; Kronbichler, Andreas; Eisenhut, Michael; Hong, Sung Hwi; van der Vliet, Hans J.; Kang, Jeonghyun; Shin, Jae Il; Gamerith, Gabriele.

In: Cancers, Vol. 11, No. 11, 1798, 11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tumor mutational burden and efficacy of immune checkpoint inhibitors

T2 - A systematic review and meta-analysis

AU - Kim, Jong Yeob

AU - Kronbichler, Andreas

AU - Eisenhut, Michael

AU - Hong, Sung Hwi

AU - van der Vliet, Hans J.

AU - Kang, Jeonghyun

AU - Shin, Jae Il

AU - Gamerith, Gabriele

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85075273184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075273184&partnerID=8YFLogxK

U2 - 10.3390/cancers11111798

DO - 10.3390/cancers11111798

M3 - Article

AN - SCOPUS:85075273184

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 11

M1 - 1798

ER -

Kim JY, Kronbichler A, Eisenhut M, Hong SH, van der Vliet HJ, Kang J et al. Tumor mutational burden and efficacy of immune checkpoint inhibitors: A systematic review and meta-analysis. Cancers. 2019 Nov;11(11). 1798. https://doi.org/10.3390/cancers11111798