Abstract B010: Tumor B8T expression stratifies overall survival in high risk muscle invasive urothelial carcinoma

• Published in: Clinical cancer research 2024-05, Vol.30 (10_Supplement), p.B010-B010
• Main Authors: Elias, Roy, Aragaki, Adam K., Hoffman-Censits, Jean H., Hahn, Noah M., McConkey, David J., Johnson, Burles A.
• Format: Article
• Language: English
• ISSN: 1557-3265; 1557-3265
• DOI: 10.1158/1557-3265.BLADDER24-B010

Background and Objective: Determining novel biomarkers to identify patients that benefit and do not benefit from immune checkpoint inhibitor (ICI) therapy is critical to avoid overtreatment. Circulating tumor DNA (ctDNA) has emerged as a biomarker that associates with overall survival (OS) benefit to ICI in patients with muscle invasive urothelial carcinoma (MIUC). However, few studies have examined whether existing immune based biomarkers stratify OS within the high risk, ctDNA(+) population. Methods: To address this, we interrogated ctDNA and RNA sequencing data from the IMvigor010 dataset of patients with high risk MIUC after cystectomy who were randomized to adjuvant atezolizumab versus observation. We correlated OS with ctDNA positivity and expression of a B cell and CD8 T cell gene signature (B8T). Key Findings: In patients who were ctDNA(+), high tumor expression of a B cell gene signature (BCGS) associated with significantly higher OS when compared with patients with low tumor BCGS, regardless of whether patients were treated with atezolizumab. In ctDNA(+) patients with high tumor expression of both BCGS and CD8 T cell gene signature (CD8TGS), e.g. B8T high/high, atezolizumab did not associate with OS benefit. Conversely, in patients with B8T high/low tumors, receipt of adjuvant atezolizumab associated with significantly increased OS (p < 0.001), and this benefit remained significant in multivariable analyses (p = 0.047). Notably, benefit with atezolizumab occurred in patients with B8T high/low tumors who were either ctDNA(+) (p = 0.057) or ctDNA(-) (p = 0.034). Conclusions and Clinical Implications: While tumor B8T high/high expression is a prognostic biomarker for OS in ctDNA(+) patients with high risk MIUC, these results suggest B8T high/low is a predictive biomarker for benefit from ICI. Moreover, in a small subset of patients who are ctDNA(-), tumor B8T high/low associates with benefit to ICI. This supports the utility of the B8T biomarker as a prognostic identifier in high risk MIUC, its ability to identify patients who will benefit from ICI regardless of ctDNA status, and for the first time ascertains a potential cohort of patients who are ctDNA(-) yet benefit from ICI. Citation Format: Roy Elias, Adam K. Aragaki, Jean H. Hoffman-Censits, Noah M. Hahn, David J. McConkey, Burles A. Johnson III. Tumor B8T expression stratifies overall survival in high risk muscle invasive urothelial carcinoma [abstract]. In: Proceedings of the AACR Special Con