Abstract 6380: Exploring immune checkpoint inhibitor-related adverse events in pediatric cancer patients: A pharmacovigilance analysis of VigiBase and the FDA adverse event reporting system (FAERS) database

Abstract

Abstract Background: With the widespread use of immune checkpoint inhibitors (ICIs) in the treatment of childhood cancers, their associated ICIs-related adverse events (irAEs) have become an important challenge. Our study was conducted to explore the pediatric high-risk ICIs-related AEs (pediatric irAEs) and explore the underlying mechanisms of pediatric irAEs. Methods: We analyzed ICIs-related adverse reaction reports in VigiBase from 1967 to 2023 and the FDA Adverse Event Reporting System (FAERS) database from 2013 to 2022. Using three methods, the reporting odds ratio (ROR), the proportional reporting ratio (PRR), and the information component (IC), we conducted a disproportionality analysis between pediatric and adult cancer patients using ICIs to discover pediatric irAEs. Furthermore, we explored the impact of clinical factors on the occurrence of pediatric irAEs and their subsequent prognosis through univariate and multivariate logistic regression analyses. Finally, combining these data with pan-cancer transcriptome data from the Gene Expression Omnibus (GEO) database, we explored the potential biological mechanisms related to pediatric irAEs. Results: We identified 4 categories of pediatric irAEs in the VigiBase and FAERS databases, including cytokine release syndrome (RORVigiBase = 17.05; RORFAERS = 14.17), acute respiratory distress syndrome (RORVigiBase = 10.26; RORFAERS = 12.39), seizure (RORVigiBase = 7.18; RORFAERS = 10.63) and febrile neutropenia (FN) (RORVigiBase = 3.01; RORFAERS = 4.84). The occurrence of pediatric irAEs may be related to mechanisms such as activation of immune cells, imbalance of inflammatory factors, activation of pathogen recognition, downregulation of inhibitory synapses, excitation/inhibition imbalance and central nervous system dysfunction. Conclusion: This study systematically analyzed the high-risk irAEs that may occur after using ICIs in pediatric cancer patients. Next, we explored the possible biological mechanisms of these pediatric irAEs to provide certain theoretical guidance for the prevention and treatment of adverse reactions in pediatric cancer patients after treatment with ICIs. Citation Format: Junyi Shen, Anqi Lin, Quan Cheng, Jian Zhang, Peng Luo. Exploring immune checkpoint inhibitor-related adverse events in pediatric cancer patients: A pharmacovigilance analysis of VigiBase and the FDA adverse event reporting system (FAERS) database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6380.