What is the burden of proof for tumor mutational burden in gliomas?

Khasraw, Mustafa, Walsh, Kyle M, Heimberger, Amy B and Ashley, David M 2021, What is the burden of proof for tumor mutational burden in gliomas?, Neuro-Oncology, vol. 23, no. 1, pp. 17-22, doi: 10.1093/neuonc/noaa256.

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Title What is the burden of proof for tumor mutational burden in gliomas?
Author(s) Khasraw, MustafaORCID iD for Khasraw, Mustafa orcid.org/0000-0003-3249-9849
Walsh, Kyle M
Heimberger, Amy B
Ashley, David M
Journal name Neuro-Oncology
Volume number 23
Issue number 1
Start page 17
End page 22
Total pages 6
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2021-01
ISSN 1522-8517
1523-5866
Keyword(s) glioblastoma
glioma
high tumor mutational burden (TMB-H)
immunobiology
immunotherapy
Summary The treatment of patients with a variety of solid tumors has benefitted from immune checkpoint inhibition targeting the anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis. The US Food and Drug Administration (FDA) granted accelerated approval of PD-1 inhibitor, pembrolizumab, for the treatment of adult and pediatric patients with high tumor mutational burden (TMB-H), solid tumors that have progressed following prior treatment, and who have no other treatment options, including the extension to tumors of the central nervous system (CNS). In general, pan-cancer approvals are viewed positively to empower patients and clinicians. There are subsets (eg, BRAF, NTRK) for which this pathway for approval is appropriate. However, the pan-cancer FDA approval of pembrolizumab raises several concerns regarding the generalizability of the evidence to other tumor types, including managing patients with gliomas and other CNS tumors. The cutoff for TMB-H is not well defined. There are intrinsic immunological differences between gliomas and other cancers types, including the immunosuppressive glioma microenvironment, the tumor’s effects on systemic immune function, and the transformation of the T-cell populations to an exhausted phenotype in glioma. Here, we address the caveats with pan-cancer approvals concerning gliomas and complexities of the unique CNS immune environment, discuss potential predictive biomarkers, including TMB, and explain why the recent approval should be applied with caution in CNS tumors.
Language eng
DOI 10.1093/neuonc/noaa256
Indigenous content off
Field of Research 1109 Neurosciences
1112 Oncology and Carcinogenesis
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30146861

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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