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Current views on tumor mutational burden in patients with non-small cell lung cancer treated by immune checkpoint
Léa Berland1,2, Simon Heeke3, Olivier Humbert4
1Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University Hospital Federation OncoAge, Antoine Lacassagne Comprehensive Cancer Center, Université Côte d'Azur, Nice, France.
Abstract:
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.
Insights
Immunotherapy improves non-small cell lung cancer (NSCLC) treatment, but response rates are low. Tumor mutational burden (TMB) shows promise as a biomarker to better select patients for immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immunotherapy targeting PD-1/PD-L1 has advanced non-small cell lung cancer (NSCLC) treatment.
- Objective response rates (ORRs) remain limited (20-30%), with significant primary resistance.
- Current PD-L1 expression biomarker for patient selection has modest sensitivity and specificity.
Purpose of the Study:
- To review recent advances in tumor mutational burden (TMB) as a predictive biomarker for immunotherapy in NSCLC.
- To discuss the challenges and future perspectives of TMB in NSCLC treatment selection.
Main Methods:
- Review of current literature on immunotherapy, PD-L1 expression, and TMB in NSCLC.
- Analysis of TMB as a predictive biomarker for immunotherapy response.
Main Results:
- TMB, defined as total nonsynonymous mutations, is an emerging biomarker for immunotherapy selection.
- TMB may complement or improve upon PD-L1 expression for identifying responsive NSCLC patients.
Conclusions:
- TMB represents a promising biomarker for optimizing immunotherapy selection in NSCLC.
- Further research is needed to overcome challenges and fully integrate TMB into clinical practice.
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