High-Grade Immune-Related Adverse Events Resulting from Immune Checkpoint Inhibitor Treatment: Evaluation of...

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but pose a risk for immune-related adverse events (IRAEs), which can be life-threatening and limit further treatment when severe. The diagnostic evaluation and management of severe IRAEs, including steroid-refractory toxicity, remains challenging. This study aims to characterize severe IRAEs (grade 3 or higher) requiring inpatient management, including toxicity grading, diagnostic evaluation, and clinical outcomes.

This single center retrospective case-review analyzed 44 patients admitted due to IRAEs. Primary cancer, toxicity grade, ICI rechallenge, lab diagnostics, and outcomes including mortality, time to treatment, additional immunomodulating agent treatment, and length of stay were evaluated.

44 patients with a total of 59 distinct IRAEs were analyzed. The median time to toxicity following ICI initiation was 18.5 weeks. The most common organ toxicities observed were colitis (n = 14), myocarditis (n = 12), and pneumonitis (n = 10) with a mean grade of 3.6. Mean time to corticosteroid treatment was 48.3 h; average length of stay was 12.2 days. Nearly one-third (31.8%) required management with immunomodulating agents in addition to corticosteroids. The most frequently elevated biomarkers were interleukin (IL)-10 (100%), C-reactive protein (CRP) (95.5%), CD25 (88.9%), and IL-6 (75%). IRAE-specific mortality was 22.7%.

Patients admitted for IRAEs tended to have high-grade toxicity and high mortality rates, highlighting the need for timely diagnostics and treatment. A cytokine signature of elevated CRP, CD25, IL-10, and IL-6 was identified and associated with IRAEs.