Immune and autoimmune-related adverse events associated with immune checkpoint inhibitors in cancer therapy

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1, known as immune checkpoint inhibitors (ICIs), have transformed cancer treatment by enhancing anti-tumor immunity.
• While effective, ICIs can disrupt self-tolerance, leading to immune-related adverse events (IRAEs), which are autoimmune conditions.
• IRAEs can affect any organ system, presenting diverse symptoms and varying in severity, sometimes leading to significant morbidity or mortality.

Purpose of the Study:

• To review the mechanisms, clinical manifestations, and management strategies for immune-related adverse events (IRAEs) associated with immune checkpoint inhibitor (ICI) therapy.
• To emphasize the importance of early recognition and prompt treatment of IRAEs for patient outcomes.
• To highlight the need for clinicians to be knowledgeable about the evolving landscape of ICI therapy and its associated toxicities.

Main Methods:

• Review of current literature on immune checkpoint inhibitors (ICIs) and their associated immune-related adverse events (IRAEs).
• Analysis of the mechanisms of action for different classes of ICIs and their distinct toxicity profiles.
• Synthesis of information regarding the clinical presentation, diagnosis, and management of IRAEs.

Main Results:

• Immune checkpoint inhibitors (ICIs) can induce a wide spectrum of immune-related adverse events (IRAEs) due to the disruption of immune self-tolerance.
• The incidence and type of IRAEs vary depending on the specific ICI agent and its mechanism of action.
• Most IRAEs are manageable with immunosuppressive therapy and supportive care, provided they are identified and treated early.

Conclusions:

• Immune checkpoint inhibitors (ICIs) represent a significant advancement in cancer therapy, but their use necessitates awareness and proactive management of immune-related adverse events (IRAEs).
• Early diagnosis and timely intervention are critical for mitigating the morbidity associated with IRAEs.
• As ICI therapy becomes more widespread, including combination approaches, comprehensive clinician education on recognizing and managing IRAEs is essential for optimizing patient care.