Blood-based tumor mutation burden: continued progress toward personalizing immunotherapy in non-small cell lung cancer

Tumor mutation burden (TMB) measures the number of somatic coding alterations in a tumor. Increased presence of these alterations contributes to immunogenicity through the generation of neoantigens targeted by T cell responses. Accordingly, a higher TMB is associated with favorable response rate and survival across multiple cancer types (1). TMB is independent of PD-L1 and is emerging as a promising immunotherapy biomarker. In non-small cell lung cancer (NSCLC), multiple studies have affirmed the utility of TMB as a marker for response to immune checkpoint inhibitors (ICI) (2-5). For example, advanced NSCLC patients with high TMB (≥10 mutations per Mb) treated with front-line combination ICI therapy had improved progression-free survival (PFS) compared to standard chemotherapy (HR 0.58, P<0.001) while patients with lower TMB did not (3).