Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_352758F0496B
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.
Journal
Annals of oncology
Author(s)
Chan T.A., Yarchoan M., Jaffee E., Swanton C., Quezada S.A., Stenzinger A., Peters S.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
Published
Issued date
01/01/2019
Peer-reviewed
Oui
Volume
30
Number
1
Pages
44-56
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required.
In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity.
High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established.
TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types.
Pubmed
Web of science
Open Access
Yes
Create date
13/11/2018 12:52
Last modification date
20/08/2019 13:22
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