In patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs), tumor mutation burden (TMB) has been found to have predictive potential for survival, according to Jinwei Zhang, PhD, from Tianjin Medical University in Tianjin, China. “When compared to TMB detection in tissue (tTMB), detecting TMB in the blood (bTMB) has practical advantages; yet, the results of various studies are conflicting,” he wrote in Frontiers in Oncology. “The question of whether bTMB can be utilized as a predictive biomarker is becoming increasingly contentious.”

The Relationship Between Immune Checkpoint Inhibitors & Tumor Mutation Burden in Blood

Dr. Zhang and colleagues conducted a systematic review and meta-analysis to investigate the relationship between ICIs and bTMB with the aim of confirming the predictive efficacy of bTMB. They systematically searched medical literature databases from inception to March 2021, focusing on the predictive value of bTMB in ICIs or the efficacy of ICIs against chemotherapy and presenting results as pooled ratio rates (RRs) and HRs with 95% CIs for the progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). The study team also performed subgroup analysis, sensitivity analysis, and heterogeneity analyses.

Across seven trials with a total of 2,610 patients with NSCLC, Dr. Zhang, et al. found no significant differences in OS (HR, 1.09; 95% CI, 0.62-1.91) or PFS (HR, 0.73; 95% CI, 0.20-2.65) between high and low bTMB groups in the ICIs cohort. When compared with chemotherapy, ICIs were found to enhance OS (HR, 0.74; 95% CI, 0.59-0.92), but improvements in PFS (HR, 0.83; 95% CI, 0.63-1.09) and ORR (RR, 0.92, 95% CI, 0.77-1.10) were only numerical trends.

Immune Checkpoint Inhibitors Better Option Than Chemotherapy for Patients With High Tumor Mutation Burden?

Patients with NSCLC treated with ICIs in the high bTMB group had better survival benefits than patients treated with chemotherapy in regard to OS (HR, 0.63; 95% CI, 0.51-0.76), PFS (HR, 0.63; 95% CI, 0.52-0.76), and ORR (RR, 1.86; 95% CI, 1.32-2.62), whereas results were similar or even reversed in the low TMB group for OS (HR, 0.89; 95% CI, 0.64-1.24), PFS (HR, 1.21, 95% CI, 0.93-1.58), and ORR (RR, 0.68, 95% CI, 0.54-0.85).

TMB could predict the enhanced survival benefit of patients with NSCLC treated with ICIs, the study authors concluded; however, the role of bTMB is limited. “For NSCLC, patients with high TMB, ICIs may be a better option than chemotherapy,” they wrote.