TMB in NSCLC: A Broken Dream?

Int J Mol Sci. 2021 Jun 18;22(12):6536. doi: 10.3390/ijms22126536.

Abstract

Although immune checkpoint inhibitors have changed the treatment paradigm of a variety of cancers, including non-small-cell lung cancer, not all patients respond to immunotherapy in the same way. Predictive biomarkers for patient selection are thus needed. Tumor mutation burden (TMB), defined as the total number of somatic/acquired mutations per coding area of a tumor genome (Mut/Mb), has emerged as a potential predictive biomarker of response to immune checkpoint inhibitors. We found that the limited use of TMB in clinical practice is due to the difficulty in its detection and compounded by several different biological, methodological and economic issues. The incorporation of both TMB and PD-L1 expression or other biomarkers into multivariable predictive models could result in greater predictive power.

Keywords: NSCLC; TMB; immune checkpoint inhibitors.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Clinical Trials as Topic
  • Disease Management
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / therapy
  • Molecular Targeted Therapy
  • Mutation*
  • Patient Outcome Assessment

Substances

  • Biomarkers, Tumor