Comprehensive management of immune-related adverse events: predictive strategies, mechanistic insights, and therapeutic approaches

Immune checkpoint inhibitors (ICIs) have been game changer in cancer therapy but can trigger diverse immune-related adverse events (irAEs) that impact multiple organs. This review offers a unified perspective on irAE risk assessment, underlying mechanisms, and therapeutic strategies aimed at maintaining anticancer efficacy while safeguarding patient well-being. We explore predictive tools-including baseline profiles of several cytokines, HLA genotype, and markers such as interleukin-6-for identifying high-risk individuals. Key drivers of irAEs were dysregulated T- and B-cell responses, antigenic cross-reactivity, and gut microbiome imbalances. Management follows a graduated approach: initial glucocorticoid intervention, followed by biologics (anti-TNF agents, IL-6 receptor blockers) or small-molecule inhibitors (JAK inhibitors) in refractory cases. Real-world data support cautious ICI use in pre-existing autoimmune disorders under stringent monitoring. We also discuss the emerging notion of "inverse irAEs," where immunosuppression may predispose to secondary malignancies, underscoring the importance of long-term surveillance. Finally, we highlight the urgent need for expansive, multicenter studies to refine irAE management to enhance therapeutic outcomes.