Dr. Dimou on Limitations of TMB as a Biomarker in Lung Cancer

Anastasios (Tassos) Dimou, MD, medical oncologist, Mayo Clinic, discusses the limitations of tumor mutational burden (TMB) as a biomarker in lung cancer.

High TMB has been shown to elicit greater response to immune checkpoint inhibitors in multiple tumor types, says Dimou. However, technical and biological limitations associated with TMB have limited its clinical utility as a biomarker in lung cancer.

Technical limitations include variations in targeted gene panel testing, preanalytical tissue fixation, and non-standardized cutoff points, explains Dimou.

Antigen presentation and the ability of the immune system to recognize and eliminate the mutated protein are biological considerations concerning TMB, says Dimou. Largely, these factors depend on human leukocyte antigen (HLA), which is often lost in patients with lung cancer.

Moreover, tumors that have loss of heterozygosity for the HLA result in defects in antigen presentation and therefore are not expected to respond to immune checkpoint inhibitors, concludes Dimou.