A comprehensive atlas of pediatric immune checkpoint inhibitors-related adverse events: From real-world pharmacovigilance data to mechanistic insights

Abstract

Background

Immune checkpoint inhibitors (ICIs) are widely used in childhood cancer, posing challenges with associated ICIs-related adverse events (irAEs). This study focuses on pediatric irAEs and explores underlying mechanisms.

Methods

Data on ICI-related adverse reactions were gathered from two sources: VigiBase database (1967–2023) and the FDA Adverse Event Reporting System (FAERS) database (2013–2022). Disproportionality analysis (Reporting odds ratio, proportional reporting ratio, information component) compared pediatric and adult cancer patients using ICIs. Integration with the Gene Expression Omnibus (GEO) database explored potential biological mechanisms.

Results

We identified four categories of pediatric irAEs in the VigiBase and FAERS databases, including cytokine release syndrome (ROR_VigiBase = 17.05; ROR_FAERS = 14.17), acute respiratory distress syndrome (ROR_VigiBase = 10.26; ROR_FAERS = 12.39), seizure (ROR_VigiBase = 7.18; ROR_FAERS = 10.63), and febrile neutropenia (FN) (ROR_VigiBase = 3.01; ROR_FAERS = 4.84). The development of irAEs in pediatric patients potentially involves various pathways: immune activation, inflammatory imbalance, pathogen recognition systems, decreased inhibitory synapses, altered E/I ratios, and CNS abnormalities.

Conclusions

This study explores pediatric irAEs, revealing potential mechanisms and stressing tailored prevention for young cancer patients on ICIs, providing theoretical insights for better management.