Discordance in Tumor Mutation Burden from Blood and Tissue Affects Association with Response to Immune Checkpoint Inhibition in Real-World Settings

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Abstract

Background: Tumor mutation burden (TMB), a biomarker for immune checkpoint inhibitor (CPI) response, is reported by both blood- and tissue-based next-generation sequencing (NGS) vendors. However, the agreement between TMB from blood (bTMB) and tissue (tTMB) in real-world settings, both in absolute value and association with CPI response, is not known. Materials and Methods: This study utilizes Sarah Cannon’s precision medicine platform, Genospace, to harmonize clinico-genomic data from 17 206 patients with cancer with NGS results from September 2015 to August 2021. A subset of patients have both bTMB and tTMB results. Statistical analyses are performed in R and include (1) correlation (r) and concordance (ρ) between patient-matched bTMB-tTMB pairs, (2) distribution of total bTMB and tTMB values, and (3) association of bTMB and tTMB with time to CPI therapy failure. Results: In 410 patient-matched bTMB-tTMB pairs, the median bTMB (m = 10.5 mut/Mb) was significantly higher than the median tTMB (m = 6.0 mut/Mb, P

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Sturgill, E. G., Misch, A., Jones, C. C., Luckett, D., Fu, X., Schlauch, D., … McKenzie, A. J. (2022). Discordance in Tumor Mutation Burden from Blood and Tissue Affects Association with Response to Immune Checkpoint Inhibition in Real-World Settings. Oncologist, 27(3), 175–182. https://doi.org/10.1093/oncolo/oyab064

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