Real-world concordance between tumor mutational burden (TMB) from blood (circulating tumor DNA) and tissue in lung cancer.
Authors: Inae Park, Jin Young Hwang, William Bae, Grace Lee, Leeseul Kim, Yoonhee Choi, Hojung Jung, Young Kwang Chae
Journal: Journal of Clinical Oncology (2021)

e20522 Background: Tumor mutational burden (TMB) level is associated with response to immunotherapy in lung cancer. However, tissue TMB can be difficult to obtain, as tissue samples obtained from biopsies may be insufficient. Circulating tumor DNA-based TMB has been developed in order to complement or replace tissue TMB, but there is limited real-world data on their concordance. Here, we investigate the landscape and concordance between blood and tissue TMB, along with clinical traits of the concordant and discordant groups. Methods: Tumor mutational burden (TMB) was calculated using Tempus (tissue) and Guardant Health (blood) next generation sequencing (NGS) platforms from October 2020 to January 2021. There were 33 patients who had both Tempus and Guardant TMB data. Under the assumption that tissue TMB (tTMB) correlates with blood TMB (bTMB) at a ratio of 1:1.6, the patients were divided into concordant and discordant groups. The concordant group patients had bTMB/tTMB ratios between 1.3 and 1.9. The discordant group was divided into two subgroups: over 1.9 (Group B) and less than 1.3 (Group C). Among the 33 patients, 9 patients were excluded due to their non-evaluable bTMB levels. Treatment response was evaluated using RECIST criteria. Results: Of the remaining 24 patients, 7 patients in the concordant group and 21 patients in the discordant group were analyzed according to their clinical manifestations [Blood TMB (n = 24): range [1.46, 44.01], median = 9.57], [Tissue TMB (n = 24), range [1.3, 18.4], median = 4.5]. We compared the clinical presentations (number of metastatic organs and metastatic sites) between the two discordant groups (Groups B and C). Among the 24 patients, 13% (n = 3) had small cell lung cancer, 50% (n = 12) had adenocarcinoma, and 29% (n = 7) had squamous cell lung carcinoma. Patients with higher bTMB than tTMB (Group B) had more squamous cell carcinoma cases (71%, n = 5) compared to remaining groups (Groups A and C) (29%, n = 2). Among the discordant group, 6% of the patients (n = 1) had small cell lung cancer, 47% (n = 8) had adenocarcinoma, and 35% (n = 6) had squamous cell carcinoma. Further, 58% (n = 14) of the patients had higher bTMB than tTMB levels. Among the concordant and discordant groups, tumor burden as reflected by the number of metastatic sites and metastatic lesions and the sum of the largest diameters of tumor lesions using RECIST had no significant difference (p = 0.10, 0.68, 0.54, respectively). The concordant and discordant groups showed no significant difference in objective response (33% vs. 20%, p = 0.60) or clinical benefit rate (100% vs. 60%, p = 0.33). Conclusions: The majority of the patients had higher blood TMB than tissue TMB (Group A), with a concordance rate as low as 28%. Further studies are warranted to understand the biology behind the difference between blood and tissue TMB, including intertumoral heterogeneity.