Multidimensional flow characterization of circulating immune cells in cisplatin-resistant metastatic urothelial cancer (mUC) patients (pts) treated with pembrolizumab (P) with or without acalabrutinib (acala).
Zhang, T; Staats, JS; Chan, C; Alva, AS; O'Donnell, PH; Harrison, MR; Batich, KA; Munugalavadla, V; George, DJ; Weinhold, KJ
Published in: Journal of Clinical Oncology
357 Background: Immunotherapy checkpoint inhibitors (ICIs) are now standard treatments (txs) in mUC, with response rates ranging 15-25%. A phase 2 randomized study (NCT02351739) treated 75 pts with mUC with either P or PA. We profiled peripheral blood mononuclear cells (PBMCs) to understand changes on tx. Methods: Comprehensive immune profiling of PBMCs was performed at baseline, weeks (wk) 4, 7, and 10. The Wilcoxon rank sum (WRS) test was used to compare tx arms, as well as pts with complete and partial response (CR/PR) vs disease progression (PD). Using the Benjamini-Hochberg (BH) method, results were deemed significant if they had false discovery rate (FDR) of 0.1 or less. Results: Clinical responses did not differ between tx arms (Zhang T et al, ESMO, 2017). The majority of patients showed largest immune changes from baseline at wk7. Comparing P vs PA pts, the PA group had statistically significant increases in PD-L1+ monocytes; CD8 T cells expressing: CD39, CTLA-4, ICOS, PD-1, TIM3, HLA-DR, Ki67, CD39/HLA-DR, CD39/Ki67, and PD-1/TIM-3; and exhausted (CD28-) CD8 T cells expressing ICOS and PD-L1 (Table). Comparing CR/PR vs PD pts, Treg subsets expressing CCR4/HLA-DR and CD39/HLA-DR were significant by WRS but not FDR criteria. Conclusions: From this extensive, exploratory, non-functional flow analysis of PBMCs, PA may potentiate immune changes of PD-L1+ monocytes and CD8+ T cell subsets. Increasing activated peripheral Tregs in CR/PR pts in either arm may indicate marginalization of Tregs from the tumor microenvironment. [Table: see text]
