Abstract 3177: Panel-derived tumor mutational burden (TMB) is associated with the response to the immune checkpoint inhibitors (ICIs) in urothelial cancers

Autor: Kien Thiam Tan, Yi-hua Jan, Yi-Lin Hsieh, Shu-Jen Chen, Pei-Ning Yu, Woei-Fuh Wang, Jen Hao Cheng, Meng-Shao Lai, Yu-Li Su, De-Wei Zhuo
Rok vydání: 2020
Předmět:
Zdroj: Cancer Research. 80:3177-3177
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2020-3177
Popis: Background: Tumor mutational burden (TMB) has been emerging as a relatively new biomarker that is independent of PDL1 for the prediction of response to the immune checkpoint inhibitor (ICI) treatment. A recent study has shown that whole exome sequencing (WES)-derived TMB correlates well with panel-derived TMB that is estimated using targeted sequencing. Here, we evaluate the correlation between panel-derived TMB with response to ICI treatment in urothelial cancers. Methods: FFPE tumor tissues from 30 patients with urothelial cancers who had previously received ICI as monotherapies or combination with chemotherapies at Chang Gung Memorial Hospital were retrospectively underwent targeted next-generation sequencing (ACTOncoTM) for the identification of nonsynonymous variants across 440 cancer- associated genes. Tumor mutational burden (TMB) was calculated by using the sequenced regions of ACTOncoTM to estimate the number of somatic nonsynonymous mutations per megabase of all protein-coding genes. The TMB calculation predicted somatic variants and applied a machine learning model with a cancer hotspot correction. RECIST criteria were used to categorize tumor response to the treatment. Results: Patients were defined as responders (CR/PR) and non-responders (SD/PD) according to the RECIST evaluation. In the cohort receiving ICI monotherapy, the responders (CR/PR, n=8) had significantly higher TMB than non-responders (SD/PD, n=15) (Median 16.2 muts/Mb vs. 6.5 muts/Mb, p=0.0035). One patient with moderate TMB (11.0 muts/Mb) who exhibited disease progression following ICI therapy harbored biallelic JAK2 inactivation. Three high-TMB tumors exhibited mutational signature of aristolochic acid exposure. Conclusions: Although the cohort size is small, this study showed that panel-derived TMB can serve as an independent predictive biomarker to identify urothelial cancer patients for immune checkpoint inhibitor therapy. Citation Format: Yi-Lin Hsieh, Pei-Ning Yu, Yi-Hua Jan, Meng-Shao Lai, Woei-Fuh Wang, De-Wei Zhuo, Shu-Jen Chen, Jen-Hao Cheng, Kien Thiam Tan, Yu-Li Su. Panel-derived tumor mutational burden (TMB) is associated with the response to the immune checkpoint inhibitors (ICIs) in urothelial cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3177.
Databáze: OpenAIRE
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