Management of immune-related adverse events associated with immune checkpoint inhibitors in cancer patients: a patient-centred approach.

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. The number of indications is increasing and antibodies targeting the CTLA-4 and PD-1/PD-L1 pathways are now also prescribed in adjuvant settings and for metastatic cancer. However, ICIs reactivate autoreactive immune cells as well as tumour-specific T cells, which lead to immune-related adverse events (irAEs) in around 70% of treated patients. Although all organs can potentially be involved, the skin, gut, thyroid, lungs, liver, and joints are most frequently affected. Most irAEs occur in the first few months of treatment but late-onset toxicity-even after the ICI has been discontinued-is also possible. In terms of severity, most irAEs are grade 1-2. Some irAEs (especially myocarditis, pneumonitis, and encephalitis) are potentially fatal; in patients with highly suggestive clinical signs, treatment should be initiated before the diagnostic work-up has been completed. When confronted with an unexpected clinical sign, the physician must differentiate rapidly between an irAE, cancer progression, and another (unrelated) cause. The management of irAEs is based on the temporary or permanent discontinuation of the ICI and (for grade ≥ 2 events) the administration of steroids.