Clinical StudiesPretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint InhibitorsMota, Jose Mauricio*; Teo, Min Yuen*; Whiting, Karissa†; Li, Han A.‡; Regazzi, Ashely M.*; Lee, Chung-Han*,‡; Funt, Samuel A.*,‡; Bajorin, Dean*,‡; Ostrovnaya, Irina†; Iyer, Gopa*,‡; Rosenberg, Jonathan E.*,‡Author Information *Genitourinary Medical Oncology Service, Departments of Medicine †Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center ‡Department of Medicine, Weill Cornell Medical College, New York, NY J.M.M. and M.Y.T. contributed equally. Present address: Jose Mauricio Mota, Sao Paulo State Cancer Institute, University of Sao Paulo, Sao Paulo, Brazil. Reprints: Min Yuen Teo, Genitourinary Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail: [email protected]). Journal of Immunotherapy: September 2021 - Volume 44 - Issue 7 - p 248-253 doi: 10.1097/CJI.0000000000000372 Buy SDC Metrics Abstract Eosinophils influence antitumor immunity and may predict response to treatment with immune checkpoint inhibitors (ICIs). To examine the association between blood eosinophil counts and outcomes in patients with advanced or metastatic urothelial carcinoma (mUC) treated with ICIs, we identified 2 ICI-treated cohorts: discovery (n=60) and validation (n=111). Chemotherapy cohorts were used as comparators (first-line platinum-based chemotherapy, n=75; second-line or more pemetrexed, n=77). The primary endpoint was overall survival (OS). Secondary endpoints were time on treatment (ToT) and progression-free survival. Univariate and multivariate analyses were performed using Cox proportional hazard models. Associations between changes in eosinophil count at weeks 2/3 and 6 after the start of ICI treatment were analyzed using landmark analyses. Baseline characteristics of the ICI cohorts were similar. In the discovery cohort, an optimal cutoff for pretreatment eosinophil count was determined [Eos-Lo: <100 cells/µL; n=9 (15%); Eos-Hi: ≥100 cells/µL; n=51 (85%)]. Eos-Lo was associated with inferior outcomes [OS: hazard ratio (HR), 3.98; 95% confidence interval (CI), 1.85–8.56; P<0.013; ToT: HR, 2.45; 95% CI, 1.17–5.10; P=0.017]. This was confirmed in the validation cohort [Eos-Lo: n=17 (15%); Eos-Hi: n=94 (85%)] (OS: HR, 2.51; 95% CI, 1.31–4.80; P=0.006; ToT: HR, 2.22; 95% CI, 1.2–3.80; P=0.004), and remained significant after adjustment for other prognostic factors. Changes in eosinophil counts at weeks 2/3 and 6 were not clearly associated with outcomes. In chemotherapy cohorts, eosinophil counts were not associated with outcomes. In conclusion, low pretreatment eosinophil count was associated with poorer outcomes in patients with mUC treated with ICIs, and may represent a new predictive biomarker. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.