Clinical and technical insights of tumour mutational burden in non-small cell lung cancer

• Published in: Critical reviews in oncology/hematology 2023-02, Vol.182, p.103891-103891, Article 103891
• Main Authors: Meri-Abad, Marina, Moreno-Manuel, Andrea, García, Sandra Gallach, Calabuig-Fariñas, Silvia, Pérez, Rafael Sirera, Herrero, Carlos Camps, Jantus-Lewintre, Eloisa
• Format: Article
• Language: English
• Subjects: B7-H1 Antigen - genetics; Biomarker; Biomarkers, Tumor - genetics; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - therapy; Humans; Immunotherapy; Lung Neoplasms - drug therapy; Lung Neoplasms - therapy; Mutation; NGS; NSCLC; TMB
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2022.103891

Despite the durable responses provided by the introduction of checkpoint inhibitors in advanced Non-Small Cell Lung Cancer (NSCLC) without actionable targets in a subset of patients, a large proportion of them will progress after immunotherapy. Programmed Death Ligand 1 (PD-L1) was the first biomarker approved for immunotherapy, although it has multiple limitations, thus the development of novel biomarkers is an urgent need. Tumour Mutational Burden (TMB) is an emerging biomarker defined as the total number of mutations per coding area of tumour genome. Targeted gene panels have emerged as a cost-effective approach to estimate TMB. However, there is still an unmet need to fully standardize sample requirements, panel size, and bioinformatic pipelines to ensure that TMB is calculated appropriately. In addition, researchers are also evaluating TMB calculation in liquid biopsy. In this work, we summarize the relevant advances and the clinical utility of TMB in NSCLC. [Display omitted] •Tumour Mutational Burden (TMB) is accurately assessed by targeted gene panels.•There is still a need for panel-based TMB harmonization and cut-off selection.•TMB is a potential useful predictive biomarker for immunotherapy in Non-Small Cell Lung Cancer.•Blood TMB has demonstrated a good correlation with tumour TMB.•More research is still needed to select the correct technological approach for blood TMB assessment.