Predictive Efficacy of Blood-Based Tumor Mutation Burden Assay for Immune Checkpoint Inhibitors Therapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Nan Zhang; Jinwei Zhang; Guoqing Wang; Xin He; Yin Mi; Ying Cao; Xiaoxu Yu

doi:10.3389/fonc.2022.795933

Predictive Efficacy of Blood-Based Tumor Mutation Burden Assay for Immune Checkpoint Inhibitors Therapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Front Oncol. 2022 Feb 9:12:795933. doi: 10.3389/fonc.2022.795933. eCollection 2022.

Authors

Nan Zhang¹, Jinwei Zhang², Guoqing Wang³, Xin He¹, Yin Mi⁴, Ying Cao¹, Xiaoxu Yu⁵

Affiliations

¹ Department of Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
² Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
³ Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, Hospital of Stomatology, Nankai University, Tianjin, China.
⁴ Department of Radiotherapy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁵ Department of Clinical Laboratory, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.

Abstract

Background: In non-small cell lung cancer (NSCLC) patients treated by immune checkpoint inhibitors (ICIs), tumor mutation burden (TMB) has been found to have predictive potential for survival. 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. The question of whether bTMB can be utilized as a predictive biomarker is becoming increasingly contentious. To confirm the predictive efficacy of bTMB, researchers did a systematic review and meta-analysis to look into the relationship between ICIs and bTMB.

Method: From the inception to March 2021, Cochrane Library, PubMed, EMBASE and other databases were systematically searched. The predictive value of bTMB in ICIs, or the efficacy of ICIs against chemotherapy, was studied. The results were presented as pooled ratio rate (RR) and hazard ratio (HR) with 95% confidence intervals for the Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Subgroup analysis, heterogeneity analyses, and sensitivity analysis were also performed.

Results: A total of 2,610 NSCLC patients were studied in seven trials. There were no significant differences in OS (HR = 1.09; 95% CI: 0.62-1.91, P = 0.774) or PFS (HR = 0.73; 95% CI: 0.20-2.65, P = 0.629) between high and low bTMB groups in the ICIs cohort. When ICIs were compared to chemotherapy, ICIs were found to enhance OS (HR = 0.74; 95% CI: 0.59-0.92, P = 0.006), but the improvement in PFS and ORR was only a numerical trend (PFS: HR = 0.83; 95% CI: 0.63-1.09, P = 0.173; ORR: RR = 0.92, 95% CI: 0.77-1.10, P = 0.372). NSCLC patients treated with ICIs in the high bTMB group had better survival benefits than chemotherapy patients in terms of OS (HR = 0.63; 95% CI: 0.51-0.76, P <0.001), PFS (HR = 0.63; 95% CI: 0.52-0.76, P <0.001), and ORR (RR = 1.86; 95% CI: 1.32-2.62, P <0.001), while in the low TMB group, the results were no different or even reversed (OS: HR = 0.89; 95% CI: 0.64-1.24, P = 0.485; PFS: HR = 1.21, 95% CI: 0.93-1.58, P = 0.154; ORR: RR = 0.68, 95% CI: 0.54-0.85, P = 0.001).

Conclusions: TMB could predict the enhanced survival benefit of NSCLC patients treated with ICIs; however the role of bTMB is limited at this stage. For NSCLC patients with high TMB, ICIc may be a better option than chemotherapy.

Keywords: immune checkpoint inhibitors (ICIs); liquid biopsy; meta-analysis; non-small cell lung cancer (NSCLC); tumor mutation burden (TMB).

Publication types

Systematic Review