Adverse Event Management in Patients Treated With Immunotherapy

Managing immune-related adverse events requires vigilant monitoring, particularly during the critical 3- to 15-week period when most toxicities emerge, potentially earlier with dual checkpoint inhibitors. Yarchoan notes that while rash often appears first, endocrinopathies including adrenal insufficiency and type 1 diabetes can occur anytime, even after a year of uneventful treatment. For people with hepatocellular carcinoma, hepatitis represents the most concerning immune-related adverse event given their already reduced liver reserve, with the challenge of distinguishing treatment-related elevation in liver function tests from tumor progression or cirrhosis deterioration.

Mahipal’s approach to elevated liver function tests involves imaging to exclude disease progression, then presuming immunotherapy-related hepatitis if cancer isn’t worsening. High-dose steroids typically serve as first-line treatment, with improvement over subsequent weeks supporting the immune-related diagnosis. Hepatology consultation provides valuable additional expertise. For refractory cases, Yarchoan adds steroid-sparing agents like mycophenolate, and occasionally tacrolimus or Janus kinase inhibitors for severe situations requiring prolonged immunosuppression management.

Retreatment after immune-related adverse events requires careful consideration, as approximately 50% of patients experience recurrence. For people who derived significant benefit, particularly near-complete responses, rechallenge may be appropriate, potentially with single-agent PD-1 rather than continuing dual checkpoint inhibition. Pneumonitis creates greater concern given life-threatening potential, while hepatitis may permit cautious retreatment depending on severity. Novel approaches include trials testing IL-6 inhibitors like tocilizumab alongside checkpoint inhibitor rechallenge, as IL-6 appears to drive immune-related adverse events. Access to specialized immune-related adverse event teams provides crucial support for managing complex cases beyond straightforward steroid-responsive toxicities.