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

doi:10.3390/cancers11111798

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

Department of Pediatrics

Research output: Contribution to journal › Article › peer-review

85 Citations (Scopus)

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 language	English
Article number	1798
Journal	Cancers
Volume	11
Issue number	11
DOIs	https://doi.org/10.3390/cancers11111798
Publication status	Published - 2019 Nov

Bibliographical note

Funding Information:
Yonsei University College of Medicine, Seoul 03722, Korea; crossing96@yonsei.ac.kr Department of Internal Medicine IV, Medical University Innsbruck, 6020 Innsbruck, Austria; andreas.kronbichler@i-med.ac.at Luton & Dunstable University Hospital NHS Foundation Trust, Luton LU4 0DZ, UK; michael_eisenhut@yahoo.com Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; sunghwihong@gmail.com Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands; jj.vandervliet@amsterdamumc.nl Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea Internal Medicine V, Department of Hematology & Oncology, Medical University Innsbruck, 6020 Innsbruck, Austria; gabriele.gamerith@i-med.ac.at Tyrolean Cancer Research Institute, 6020 Innsbruck, Austria Correspondence: ravic@naver.com (J.K.); shinji@yuhs.ac (J.I.S.); Tel.: +82-2-2019-3369 (J.K.); +82-2-2228-2050 (J.I.S.)

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers11111798

Cite this

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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",

note = "Funding Information: Yonsei University College of Medicine, Seoul 03722, Korea; crossing96@yonsei.ac.kr Department of Internal Medicine IV, Medical University Innsbruck, 6020 Innsbruck, Austria; andreas.kronbichler@i-med.ac.at Luton & Dunstable University Hospital NHS Foundation Trust, Luton LU4 0DZ, UK; michael_eisenhut@yahoo.com Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; sunghwihong@gmail.com Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands; jj.vandervliet@amsterdamumc.nl Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea Internal Medicine V, Department of Hematology & Oncology, Medical University Innsbruck, 6020 Innsbruck, Austria; gabriele.gamerith@i-med.ac.at Tyrolean Cancer Research Institute, 6020 Innsbruck, Austria Correspondence: ravic@naver.com (J.K.); shinji@yuhs.ac (J.I.S.); Tel.: +82-2-2019-3369 (J.K.); +82-2-2228-2050 (J.I.S.) Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

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language = "English",

volume = "11",

journal = "Cancers",

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AU - Hong, Sung Hwi

AU - van der Vliet, Hans J.

AU - Kang, Jeonghyun

AU - Shin, Jae Il

AU - Gamerith, Gabriele

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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.

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Tumor mutational burden and efficacy of immune checkpoint inhibitors: A systematic review and meta-analysis

Abstract

Bibliographical note

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UN SDGs

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