Abstract 3376: Non-small cell lung cancer (NSCLC) with higher blood tumor mutational burden (bTMB)/tissueTMB (tTMB) ratio is associated with inferior survival outcome
Authors: Kim Leeseul , Park Jewel , Oh Youjin , Chae Young Kwang 
Published: April 2023

Background: High TMB is known to correlate with better response to immune checkpoint inhibitor (ICI) treatment in certain cancers. bTMB is now being used in place of tTMB at times due to difficulty in obtaining enough tissue samples for sequencing. Concordance between bTMB and tTMB values has been reported. However, the prognostic role of bTMB in relation to tTMB is not well understood.

Method: Patients with NSCLC who had both tTMB and bTMB results (collected from 10/2020 to 10/2022) were included. Progression free survival (PFS) and overall survival (OS) were analyzed according to bTMB, tTMB levels (High defined as ≥ 10 Mut/Mb, Low defined as &lt;10 Mut/Mb), and bTMB/tTMB ratio. The Gehan-Breslow-Wilcoxon test was used for survival analysis and the Mantel-Haenszel test was used to calculate the hazard ratio. Survival analysis by bTMB was performed only in 40 patients where bTMB was collected before and within 30 days of treatment initiation.

Results: Among 61 pts,18 pts (29%) received ICI monotherapy, 25 pts (41%) received ICI and chemotherapy combination therapy, 8 pts (14%) received chemotherapy, and 10 pts (16%) received targeted therapy. The median interval between bTMB collection and treatment initiation was 20 days (Q1:11, Q3:47) while 40 pts (66%) had the interval of &lt;30 days. 12 pts (20%) were tTMB high, and 32 pts (52%) were bTMB high. There was no difference in OS between groups with tTMB high and low. Similar findings were seen in OS and PFS of pts who received ICI containing regimen (p-value 0.71, 0.59, and 0.18, respectively). Group with high bTMB showed inferior OS compared to the group with low bTMB(p=0.008, OS HR=4.4) regardless of treatment regimens. Among people treated with ICI containing regimen, a similar trend was seen (p=0.009, OS HR=4.9). The median bTMB/tTMB ratio was 2.49. Patients were divided into three groups according to bTMB/tTMB tertiles (1st: 0.31-1.62, 2nd: 1.71-3.65, 3rd: 3.86-11.48). There was a significant difference in OS among the three groups with the 3rd tertile having the worst prognosis (log-rank test for trend, p=0.04). When divided into two groups (1st+2nd vs 3rd), the 3rd tertile group had a significantly inferior OS (p=0.01, HR 5.58). Among people treated with ICI containing regimen, a trend toward inferior OS was seen in the 3rd tertile group (p=0.12, HR 3.03). However, no significant difference in PFS was seen (p-value 0.77, HR 1.05).

Conclusion: High bTMB/tTMB ratio was associated with inferior OS regardless of treatment regimen in patients with NSCLC. A high bTMB/tTMB ratio may be indicative of increased tumor heterogeneity and/or higher metastatic tumor burden. Further studies are warranted to explore the role of bTMB/tTMB in various cancers.

Citation Format: Leeseul Kim, Jewel Park, Youjin Oh, Young Kwang Chae. Non-small cell lung cancer (NSCLC) with higher blood tumor mutational burden (bTMB)/tissueTMB (tTMB) ratio is associated with inferior survival outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3376.