Current views on tumor mutational burden in patients with non-small cell lung cancer treated by immune checkpoint inhibitors
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In the last few years, the treatment of patients with non-small cell lung cancer (NSCLC) has impressively benefitted from immunotherapy, in particular from the inhibition of immune checkpoints such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1). However, despite the significant survival benefit for some patients with advanced NSCLC, the objective response rates (ORRs) remain relatively low no more than 20-30% with a large proportion of patients demonstrating primary resistance. Although the selection of NSCLC patients for the first-line treatment is currently guided by the expression of PD-L1 in tumor cells as detected by immunohistochemistry, this is not the case for the second-line setting. Moreover, the sensitivity and specificity of PD-L1 expression is modest which has prompted the search for additional predictive biomarkers. In this context, the assessment of the tumor mutational burden (TMB), defined as the total number of nonsynonymous mutations in the coding regions of genes, has recently emerged as an additional powerful biomarker to select patients for immunotherapy. The purpose of our review is to highlight the recent advances as well as the challenges and perspectives in the field of TMB and immunotherapy for patients with NSCLC.
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In patients with NSCLC, if TMB was equal to or greater than 10 mut/Mb, the combination of nivolumab and ipilimumab would have a better overall response regardless of PD-L1 expression.
“In patients with NSCLC, it was reported that if TMB was equal to or greater than 10 mut/Mb, the combination of Nivolumab and Ipilimumab would have a better overall response (OR) regardless of PD-L1 expression [109].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [109]
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Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
- Authors
- Berland, L., Heeke, S., Humbert, O., Macocco, A., Long-Mira, E., Lassalle, S., Lespinet-Fabre, V., Lalvée, S., Bordone, O., Cohen, C., Leroy, S., Hofman, V., Hofman, P., & Ilié, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Côte d'Azur (FR)
- Corresponding author
- Ilié, Marius
- ORCID
- Venue
- Journal of Thoracic Disease
- Publisher
- AME Publishing Company
- Published
- 2019-01
- Volume
- 11
- Issue
- S1
- Pages
- S71-S80
- ISSN
- 2072-1439 (ISSN-L)
- 2077-6624
- PMC
- PMC6353746
- OpenAlex
- W2902389984
- Cited by
- 95
- References
- 54
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 11 · 2022: 12 · 2021: 27 · 2020: 29 · 2019: 4 · 2018: 1 · 2013: 1
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Thoracic Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-LABX-0028)
- Canceropôle PACA
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- tumor mutational burden, non-small cell lung cancer, immune checkpoint inhibitors, PD-1, PD-L1, predictive biomarkers, immunotherapy, primary resistance, second-line therapy, non-synonymous mutations
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