학술논문
Baseline Circulating Blood Cell Counts and Ratios and Changes Therein for Predicting Immune-Related Adverse Events during Immune Checkpoint Inhibitor Therapy: A Multicenter, Prospective, Observational, Pan-Cancer Cohort Study with a Gender Perspective
Document Type
Clinical report
Author
Source
Cancers. December 2023, Vol. 16 Issue 1
Subject
Language
English
ISSN
2072-6694
Abstract
Author(s): Lucía Teijeira [1]; Mireia Martínez [2,3]; Amaia Moreno [4]; Ibone de Elejoste [5]; Berta Ibáñez-Beroiz [6]; Virginia Arrazubi [1]; Isabela Díaz de Corcuera [4]; Iñaki Elejalde [7,8,9]; Ana Campillo-Calatayud [...]
The growing use of immune checkpoint inhibitors (ICIs) for the treatment of patients with solid tumors has led to a proportional increase in the incidence of toxic effects in the form of immune-related adverse events (irAEs). In this study, we show that two readily available blood cell parameters, namely, high absolute lymphocyte count before ICI initiation and early decline in absolute neutrophil count after ICI initiation, can predict irAEs during follow-up. Interestingly, however, the predictive ability of both pre-ICI absolute lymphocyte count and post-ICI absolute neutrophil count differ significantly between men and women. In the prediction of irAEs, we also describe an interaction between female gender and a decrease in absolute neutrophil count after the first cycle of ICI therapy. These findings should lead to the development of new predictive models for irAEs that are able to capture sex-related differences in ICI-induced toxicity. Several factors have been associated with the occurrence of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) therapy. Despite their availability, the predictive value of circulating blood cell parameters remains underexplored. Our aim was to investigate whether baseline values of and early changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC), other blood cell counts, and lymphocyte-related ratios can predict irAEs and whether sex may differentially influence this potential predictive ability. Of the 145 patients included, 52 patients (35.8%) experienced at least one irAE, with a 1-year cumulative incidence of 41.6%. Using Fine and Gray competing risk models, we identified female sex (hazard ratio (HR) = 2.17, 95% confidence interval (CI) = 1.20–3.85), high ALC before ICI initiation (HR = 1.63, 95% CI = 1.09–2.45), and low ANC after ICI initiation (HR = 0.81, 95% CI = 0.69–0.96) as predictors of irAEs. However, ALC and ANC may only have an impact on the risk of irAEs in women (stratified for female sex, ALC-related HR = 2.61, 95% CI = 1.40–4.86 and ANC-related HR = 0.57, 95% CI = 0.41–0.81). Priority should be given to developing models to predict ICI-related toxicity and their validation in various settings, and such models should assess the impact of patient sex on the risk of toxicity.
The growing use of immune checkpoint inhibitors (ICIs) for the treatment of patients with solid tumors has led to a proportional increase in the incidence of toxic effects in the form of immune-related adverse events (irAEs). In this study, we show that two readily available blood cell parameters, namely, high absolute lymphocyte count before ICI initiation and early decline in absolute neutrophil count after ICI initiation, can predict irAEs during follow-up. Interestingly, however, the predictive ability of both pre-ICI absolute lymphocyte count and post-ICI absolute neutrophil count differ significantly between men and women. In the prediction of irAEs, we also describe an interaction between female gender and a decrease in absolute neutrophil count after the first cycle of ICI therapy. These findings should lead to the development of new predictive models for irAEs that are able to capture sex-related differences in ICI-induced toxicity. Several factors have been associated with the occurrence of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) therapy. Despite their availability, the predictive value of circulating blood cell parameters remains underexplored. Our aim was to investigate whether baseline values of and early changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC), other blood cell counts, and lymphocyte-related ratios can predict irAEs and whether sex may differentially influence this potential predictive ability. Of the 145 patients included, 52 patients (35.8%) experienced at least one irAE, with a 1-year cumulative incidence of 41.6%. Using Fine and Gray competing risk models, we identified female sex (hazard ratio (HR) = 2.17, 95% confidence interval (CI) = 1.20–3.85), high ALC before ICI initiation (HR = 1.63, 95% CI = 1.09–2.45), and low ANC after ICI initiation (HR = 0.81, 95% CI = 0.69–0.96) as predictors of irAEs. However, ALC and ANC may only have an impact on the risk of irAEs in women (stratified for female sex, ALC-related HR = 2.61, 95% CI = 1.40–4.86 and ANC-related HR = 0.57, 95% CI = 0.41–0.81). Priority should be given to developing models to predict ICI-related toxicity and their validation in various settings, and such models should assess the impact of patient sex on the risk of toxicity.