MP49-03: Circulating Tumor Cell Subtypes and Baseline T-cell Population as Prognostic Biomarkers to Combination Therapy with Cabozantinib, Nivolumab, and Ipilimumab in Metastatic Genitourinary Cancer Patients

Heather Chalfin, Amir Mortazavi, Scot Niglio, Joseph Schonhoft, Tiziano Pramparo, Adam Jendrisak, Lincy Chu, Jiyun Byun, Amanda Anderson, Yipeng Wang, Ryan Dittamore, Sumanta Pal, Primo Lara, Mark Stein, Seth Steinberg, Lisa Cordes, Lisa Ley, Marissa Mallek, Olena Sierra Ortiz, Rene Costello, Jacqueline Cadena, Carlos Diaz, Jane Trepel, Don Bottaro, Andrea Apolo

Introduction: Circulating tumor cells (CTCs) are currently under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection.  Beyond enumeration, CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. Here, we compared CTC features and T-cell activation with overall survival (OS) in a cohort of metastatic genitourinary cancer (mGU) patients treated with immunotherapy combination (Trial ID NCT02496208).

Methods: 139 samples from N=61 mGU patients undergoing cabozantinib + nivolumab +/- ipilimumab therapy (phase 1) were collected at baseline and on-therapy. Slides were processed with the Epic platform (pan-CK/CD45/PD-L1/DAPI for CTCs; CD4/CD8/Ki-67/DAPI for T-Cells). Approximately 3 million cells per slide were imaged to detect and assess CTC burden, as well as to quantify changes in immune cell populations.

Results: From 12/2016-01/2019, 61 patients [urothelial N = 39; bladder plasmacytoid N = 1; clear cell renal cell N = 4; bladder adenocarcinoma/urachal N = 8; bladder squamous N = 3; bladder small cell N = 2; renal medullary carcinoma N = 2; penile cancer N=2] were treated. CTCs were found in 70% of patients at baseline and Cycle 2. At Cycle 2, CTC burden was associated with shorter OS (5.1 vs 24.7 months, p = 0.015), and the presence of two specific CTC subtypes were also associated with shorter OS (2.27 vs 19.53 months, 1.71 vs 24.69 months, p<0.0001, p=0.0059). Features associated with these two subtypes included CK intensity and speckling, circularity, cell size and nucleoli count. Similar trends were observed with progression free survival.  Low baseline CD4 and CD8 counts were also associated with poor OS (%CD4<7 p=0.0001, %CD8<3 p=0.024).

Conclusions: Shorter survival is associated with high CTC counts at Cycle 2, presence of specific CTC subtypes on therapy, and low %CD4 and %CD8 T-cells in mGU cancer patients. Ongoing efforts include digital pathology analysis of T-cell populations and single cell sequencing of CTC subtypes, as well as analysis of an additional 19 patients. Source of

Funding: This project has been funded with federal funds from the National Cancer Institute, National Institutes of Health