Long-Term Toxicities of Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) produce often durable responses in many cancer types but are associated with autoimmune-like toxicities. These immune-related adverse events (irAEs) occur in multiple organ systems and often improve with steroids or therapy cessation. However, many irAEs have either partial or no improvement, leading to residual sequelae even after ICI discontinuation. Chronic irAEs, often defined as irAEs lasting > 3 months, may occur in up to 40-50% of patients treated with ICI therapy and have a wide range of manifestations, severity, and duration. These chronic events likely stem from either ongoing inflammation or sequalae of prior inflammatory-mediated damage. IrAEs impacting the endocrine glands and joints have particularly high rates of chronicity, while chronic events impacting the gastrointestinal (GI) tract, liver, and lungs are less common. In this review, we discuss updated studies surrounding chronic irAEs, providing an overview, followed by organ-specific considerations and consideration of future directions. Key challenges for the field include characterizing the chronic impact of irAEs, developing better treatment or prevention strategies (one possible solution being anti-cytokine therapy), and identifying which patients have active inflammation.