Clinical sequencing to assess tumor mutational burden as a useful biomarker to immunotherapy in various solid tumors

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become established as a new therapeutic paradigm in various solid cancers. Predictive biomarkers to ICIs have not yet been fully established. Tumor mutational burden (TMB) has been considered as a useful marker to indicate patients who benefit from ICIs. METHODS: We performed next-generation sequencing, including TMB analysis, as a routine clinical practice in 501 patients with advanced gastrointestinal (GI), genitourinary (GU), or rare cancers. The TruSight(™) Oncology 500 assay from Illumina was used as a cancer panel. RESULTS: In total, 11.6% (58/501) were identified with tumors with high TMB and MSI-high status was confirmed in seven out of 501 cases (1.4%). High TMB was observed in 11.6% of patients with various solid tumors, including: GU cancers (36.0%, 9/25), colorectal cancer (15.2%, 23/151), biliary tract cancer (14.6%, 7/48), melanoma (14.3%, 3/21), gastric cancer (11.2%, 13/116), hepatocellular carcinoma (8.3%, 1/12), other GI tract cancers (4.5%, 1/22), and sarcoma (1.7%, 1/60). The objective response rate (ORR) to ICIs was 75% (nine out of 12) in solid tumor patients with high TMB and 25% (30 out of 40) in those with non-high TMB. Patients with high TMB had better ORR to ICIs than those with non-high TMB (p = 0.004). Univariate analysis revealed that the status of PD-L1 expression and of TMB (high versus non-high) had significant association in response to ICIs. However, in multivariate analysis, the status of TMB (high versus non-high) was only significantly related to the response to ICIs (p = 0.036). CONCLUSION: In the present study, we analyzed the TMB using a cancer panel for various solid tumor patients in routine clinical practice and also demonstrated the usefulness of TMB to predict the efficacy for ICIs.