Tumor Mutation Burden as a Potential Biomarker for PD-1/PD-L1 Inhibition in Advanced Non-small Cell Lung Cancer
Di Huang1,2, Fan Zhang2, Haitao Tao2
1School of Medicine, Nankai University, 94 Weijin Road, Nankai, Tianjin, 300071, People's Republic of China.
Background:
Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are reported to benefit from PD-1/PD-L1 inhibitors. However, additional biomarkers are needed, and whether tumor mutation burden (TMB) can be a robust biomarker or not is still controversial.
Objective:
We conducted this study to assess TMB as a biomarker for PD-1/PD-L1 inhibitor treatment in advanced NSCLC patients in a real-world setting.
Patients And Methods:
Chinese NSCLC patients who received a PD-1/PD-L1 inhibitor at the People's Liberation Army General Hospital and who had pathological tissues available for TMB were retrospectively analyzed. Demographic and clinical information were evaluated. Targeted next-generation sequencing (NGS) of the tumor tissue was performed. The relationship between TMB and clinical benefit was assessed.
Results:
Thirty-four patients treated with PD-1/PD-L1 inhibitors between March 2015 and January 2019 were analyzed. The TMB was greater in patients with complete response (CR)/partial response (PR) versus stable disease (SD) versus progressive disease (PD) (median 11 vs. 9.7 vs. 4.2 mutations/megabase [Mb]; p = 0.049). The median progression-free survival was 10.6 months in the TMB-high group versus 3.9 months in the TMB-low group (cut-off value = 10 mutations/Mb) (hazard ratio [HR] 0.26 [95% confidence interval 0.12-0.57], p = 0.0007). The median overall survival was 21.0 months and 11.6 months (HR 0.37 [0.17-0.81], p = 0.0126) in the TMB-high group and the TMB-low group, respectively. The disease control rate was higher in the TMB-high group than in the TMB-low group (100% vs. 70%, p = 0.024).
Conclusions:
High TMB was associated with a better outcome in advanced NSCLC patients who received PD-1/PD-L1 inhibitors in China. Further studies are needed to confirm our findings.
Insights
High tumor mutation burden (TMB) in non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors correlates with better outcomes. This real-world study in China suggests TMB is a promising biomarker for immunotherapy effectiveness.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immunotherapy using PD-1/PD-L1 inhibitors has transformed non-small cell lung cancer (NSCLC) treatment.
- High PD-L1 expression or dMMR/MSI-H status predicts response to these inhibitors.
- The utility of tumor mutation burden (TMB) as a predictive biomarker remains debated.
Purpose of the Study:
- To evaluate tumor mutation burden (TMB) as a biomarker for PD-1/PD-L1 inhibitor efficacy in advanced NSCLC patients.
- To assess the relationship between TMB and clinical benefit in a real-world setting.
Main Methods:
- Retrospective analysis of Chinese NSCLC patients treated with PD-1/PD-L1 inhibitors.
- Targeted next-generation sequencing (NGS) of tumor tissue to determine TMB.
- Correlation analysis between TMB levels and clinical outcomes (response, survival, disease control).
Main Results:
- Higher TMB was observed in patients achieving complete or partial response compared to stable or progressive disease (median 11 vs. 9.7 vs. 4.2 mutations/Mb).
- TMB-high patients demonstrated significantly longer median progression-free survival (10.6 vs. 3.9 months) and overall survival (21.0 vs. 11.6 months).
- The disease control rate was higher in the TMB-high group (100%) versus the TMB-low group (70%).
Conclusions:
- Elevated tumor mutation burden (TMB) is associated with improved outcomes in advanced NSCLC patients receiving PD-1/PD-L1 inhibitors.
- TMB shows potential as a predictive biomarker for immunotherapy response in this patient population.
- Further research is warranted to validate these findings in larger cohorts.
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