Exploring real-world concordance of tissue mutation burden (TMB) from blood and tissue in patients with solid tumors

Purpose Tumor mutational burden (TMB) is an approved biomarker for immunotherapy in metastatic cancer patients. While initially measured from tissue (tTMB), TMB derived from circulating tumor DNA (ctDNA) - also known as blood TMB (bTMB) - is increasingly being used in the clinic. Currently, real-world concordance between tTMB and bTMB is not well understood. Patients and methods From October 2020 to March 2021, cancer patients who had both tTMB and bTMB results were selected. Patients were classified according to clinical variables and tumor burden, and correlation analyses or tests of independence were performed to explore any associations. Results From a total of 38 patients included in our study, 20 patients (52.6%) had non-small cell lung carcinoma and 18 (47.4%) had other cancers. Median bTMB of 9.6 mut/MB was higher than median tTMB of 4.0 mut/Mb, and the distributions of bTMB and tTMB differed significantly (n=38, p < 0.001). bTMB was positively correlated with tTMB in the total study population (Spearman ρ=0.57, p < 0.001 ) and a tTMB of 10 mut/Mb correlated with a bTMB of 21.1 mut/Mb. Dividing patients by cancer type or site of tumor biopsy resulted in significantly differing strength and degree of correlation, but dividing patients by concordant and discordant bTMB:tTMB ratio did not reveal any significantly different distributions of clinical variables or tumor burden. Conclusion bTMB was positively correlated with tTMB, and median bTMB was higher than median tTMB. Cancer type and site of tissue biopsy may influence concordance between tTMB and bTMB. Future studies with more patients may help define the optimal bTMB threshold for receiving immunotherapy, which may be different from the tTMB threshold.