Blood Tumor Mutational Burden as a Predictive Biomarker in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Abstract

This study was designed to investigate the impact of blood tumor mutational burden (bTMB) on advanced NSCLC in Southwest China. The relationship between the tTMB estimated by next-generation sequencing (NGS) and clinical outcome was retrospectively analyzed in tissue specimens from 21 patients with advanced NSCLC. Furthermore, the relationship between the bTMB estimated by NGS and clinical outcome was retrospectively assessed in blood specimens from 70 patients with advanced NSCLC. Finally, 13 advanced NSCLC patients were used to evaluate the utility of bTMB assessed by NGS in differentiating patients who would benefit from immunotherapy. In the tTMB group, tTMB ≥ 10 mutations/Mb was related to inferior progression-free survival (PFS) (hazard ratio [HR], 0.30; 95% CI, 0.08-1.17; log-rank P = 0.03) and overall survival (OS) (HR, 0.30; 95% CI, 0.08-1.16; log-rank P = 0.03). In the bTMB group, bTMB ≥ 6 mutations/Mb was associated with inferior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank P < 0.01) and OS (HR, 0.31; 95% CI, 0.14-0.7; log-rank P < 0.01). In the immunotherapy section, bTMB ≥ 6 mutations/Mb was related to superior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank P < 0.01) and objective response rates (ORRs) (bTMB < 6: 14.2%; 95% CI, 0.03-1.19; bTMB ≥ 6: 83.3%; 95% CI, 0.91-37.08; P = 0.02). These findings suggest that bTMB is a validated predictive biomarker for determining the clinical outcome of advanced NSCLC patients and may serve as a feasible predictor of the clinical benefit of immunotherapies (anti-PD-1 antibody) in the advanced NSCLC population in Yunnan Province.

Multi-Omics Approaches for the Prediction of Clinical Endpoints after Immunotherapy in Non-Small Cell Lung Cancer: A Comprehensive Review

“…The assessment of the blood tumor mutation burden (bTMB) has the advantage of a non-invasive approach with much less evaluation. In a small set of 42 patients, bTMB was significantly correlated with progression-free survival [ 33 ], conforming with similar results [ 34 , 35 , 36 ]. DNA methylation also appears as an efficient prediction tool in NSCLC, with the benefit of a better understanding of the underlying molecular determinants [ 37 , 38 , 39 ].…”

On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial

“…Wang et al showed that modified bTMB could identify patients who derive clinically significant improvements in PFS from anti–PD-(L)1 monotherapy in advanced NSCL C[ 18 ]. More recently, two retrospective studies found that bTMB can serve as a potential biomarker for predicting the efficacy of ICIs alone in NSCL C[ 36 , 37 ]. However, whether bTMB could serve as a predictor for immunotherapy plus chemotherapy remains unknown.…”

The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer

“…There are some discrepancies between clinical thresholds for bTMB and tTMB in NSCLC patients. For instance, Ttmb > 10 mutations/Mb was associated with a shorter PFS and OS during the implementation of ICIs, while a similar relationship was observed for bTMB > 6 mutations/Mb [ 142 ]. However, a low level of bTMB was insignificantly correlated with longer PFS or OS in NSCLC patients treated with ICIs, while NSCLC patients with high bTMB may benefit from ICIs compared to patients who received chemotherapy [ 143 , 144 ].…”