Pretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors.
Aged
B7-H1 Antigen
/ antagonists & inhibitors
Eosinophils
/ immunology
Female
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Kaplan-Meier Estimate
Leukocyte Count
Male
Middle Aged
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Proportional Hazards Models
Retrospective Studies
Treatment Outcome
Urologic Neoplasms
/ drug therapy
Urothelium
/ pathology
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
Titre abrégé: J Immunother
Pays: United States
ID NLM: 9706083
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
received:
20
01
2021
accepted:
29
03
2021
pubmed:
4
6
2021
medline:
22
3
2022
entrez:
3
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34081050
doi: 10.1097/CJI.0000000000000372
pii: 00002371-202109000-00002
pmc: PMC8373810
mid: NIHMS1700609
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
Immune Checkpoint Inhibitors
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
248-253Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221745
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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