Diagnosis and Management of Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy

The landscape of cancer therapy has undergone a profound transformation in the last decade, shifting from traditional cytotoxic chemotherapy to the rapid rise of immune checkpoint inhibitor (ICI) therapy and combination treatments, fundamentally altering the approach to cancer treatment. However, these advancements introduce challenges in the form of unique toxicities and heightened morbidity. Unlike the side effects associated with conventional chemotherapy, ICI therapy-induced toxicity stems from the over-activation of the immune system, exhibiting delayed onset and persisting for months after treatment cessation. Prompt recognition and intervention are crucial to mitigate associated morbidity and mortality. The FDA has approved ICI drugs targeting four immune checkpoints, including CTLA-4, PD-1, PD-L1, and LAG-3, with dual therapy commonly involving anti-CTLA-4 concurrently with PD-1 or PD-L1 inhibitors. Despite variations in immune system targets, immunotherapy agents share similar and overlapping side effect profiles, necessitating a universal approach to treating immune-related adverse events (irAEs). These events, classified by organ system and severity, commonly impact dermatologic, gastrointestinal, and endocrine systems. While less frequent, toxicities affecting pulmonary, neurologic, and cardiac systems are often more severe, requiring a delicate balance in managing irAEs to attenuate immune response while preserving antitumor efficacy.