Pretreatment eosinophil counts (PEC) in metastatic urothelial carcinoma (mUC) treated with anti-PD1/PD-L1 checkpoint inhibitors (CPI).

Jose Mauricio Mota Memorial Sloan-Kettering Cancer Center, New York, NY info_outline Jose Mauricio Mota, Min Yuen Teo, Karissa Whiting, Irina Ostrovnaya, Han Li, Chung-Han Lee, Samuel Aaron Funt, Margaret K. Callahan, Gopa Iyer, Dean F. Bajorin, Jonathan E. Rosenberg

Authors Jose Mauricio Mota Memorial Sloan-Kettering Cancer Center, New York, NY info_outline Jose Mauricio Mota, Min Yuen Teo, Karissa Whiting, Irina Ostrovnaya, Han Li, Chung-Han Lee, Samuel Aaron Funt, Margaret K. Callahan, Gopa Iyer, Dean F. Bajorin, Jonathan E. Rosenberg Organizations Memorial Sloan-Kettering Cancer Center, New York, NY, Memorial Sloan Kettering Cancer Center, New York, NY, Weill Cornell Medicine, New York, NY, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY Abstract Disclosures Research Funding Other Background: Eosinophils may influence anti-tumor immunity, having been associated with outcomes in CPI-treated melanoma. We sought to examine the association between PEC and outcomes of CPI-treated mUC. Methods: Independent CPI-treated cohorts were identified: discovery (n = 60, Teo et al JCO 2018) and validation (n = 111, non-overlapping CPI-treated mUC patients [pts] from 2014-19). Uni- and multivariate analyses were performed using Cox proportional hazard models to evaluate prognostic value of PEC on (i) overall survival (OS) and (ii) time on treatment (ToT). A platinum-treated metastatic cohort (n = 81, Teo et al, CCR 2017) was used as non-CPI comparator. Results: The cohorts showed comparable OS and pts characteristics, except higher proportion of females and lower neutrophil at baseline (Neut) in the validation cohort. In the discovery cohort, PEC as a continuous variable showed a significant positive association with OS (HR 0.01, 95% CI 0.00-0.29, P = .009). PEC of 100 cells/µL was set as the optimal cut-off point (Eos-L: < 100 cells/µL, n = 9; Eos-H: ≥100 cells/µL, n = 51). Eos-L showed inferior outcomes (OS: HR 3.98, 95%CI 1.85-8.56, P < .001; ToT: HR 2.45, 95%CI 1.17-5.10, P = .017). Similar association was seen in the validation cohort (Eos-L, n = 17; Eos-H, n = 94; OS: HR 2.51, 95%CI 1.31-4.80, P = .006; ToT: HR 2.22, 95%CI 1.29 - 3.80, P = .004). A multivariate model adjusting for other prognostic variables was created (table). In the chemotherapy cohort, continuous Eos or Eos-L was not associated with OS/ToT, with or without adjusting for known prognostic factors (P > 0.5). Conclusions: The association between Eos-L and shorter OS in CPI- but not chemotherapy-treated cohorts might represent a potential negative predictive biomarker for CPI in mUC. Discovery Validation HR 95% CI P HR 95% CI P OS Eos-L vs Eos-H 3.17 1.42-7.05 0.005 2.26 1.32-4.85 0.003 DDR mut* 0.34 0.17-0.70 0.003 0.79 0.58-1.74 0.245 Neut # 1.11 1.00-1.22 0.040 1.00 0.97-1.11 0.888 ToT Eos-L vs Eos-H 1.53 0.68-3.42 0.300 2.26 1.31-3.89 0.003 DDRmut* 0.38 0.21-0.71 0.002 0.79 0.54-1.17 0.245 Neut # 1.17 1.07-1.28 0.001 1.00 0.95-1.06 0.888 * DDRmut: Mutations in DNA damage repair genes; # as continuous variable