Serial changes in PD1/PDL1 expression in metastatic urothelial carcinoma (mUC) patients (pts) treated with immune checkpoint blockade (CPB).

Abstract

109 Background: Since CPB may alter immune marker expression in key immunomodulatory populations such as myeloid-derived suppressor cells (MDSC) and CD8+ cytotoxic T lymphocytes (CTL), we evaluated PD1/PDL1 expression in longitudinal samples from mUC pts treated with CPB. Methods: Serial peripheral blood samples were collected from mUC pts who received CPB. PD1/PDL1 and VISTA expression was measured in MDSC (CD33+HLADR−) and CTL (CD8+CD4−) from live peripheral blood mononuclear cells using flow cytometry. MDSC subsets were further defined as (G)ranulocytic (CD15+CD14−), (M)onocytic (CD15−CD14+), and (I)mmature (CD15−CD14−). PD1/PDL1 and VISTA expression was presented as % of each MDSC subset or CTL. Wilcoxon signed-rank tests and mixed-model regression analyses were performed to assess changes in immune marker expression after CPB. Results: Of 30 CPB-treated pts with ≥ 2 blood samples for analysis, 21 received anti-PDL1 (20 atezolizumab/1 avelumab; [A]) and 9 received anti-PD1 (pembrolizumab [P]). Median age at diagnosis was 69.5 (46–81), 77% men, 33% never smokers, 63% pure UC, 70% bladder primary, 20% prior intravesical BCG, 37% prior neoadjuvant chemotherapy, 63% prior cystectomy. Best overall responses to CPB were 3 PR/13 SD/5 PD (A) and 1 CR/1 PR/4 SD/3 PD (P). Successive doses of A correlated with decreased %PDL1+ M-MDSC, while those of P correlated with decreased %PD1+ M- and I- MDSC (Table). No significant changes in VISTA expression were detected. In 11 A-treated pts with samples before/after the 1st dose, %PDL1+ M- and I- MDSC decreased (median change −25.5 and −5.7; p = 0.02 and 0.03) and %PD1+ CTL increased (median change +2.4; p = 0.02) between 1st and 2nd samples. Conclusions: In this mUC pt cohort, distinct post-tx changes in %PD1/PDL1 in MDSC subsets and CTL occurred based on CPB (anti-PD1 vs anti-PDL1). Further analysis of correlations between CPB, immune marker expression, clinicopathologic factors, and outcomes is ongoing in a larger cohort. Mean absolute change in marker expression per dose in pts treated with CPB. [Table: see text]