Association of Rare Immune-Related Adverse Events to Survival in Advanced Cancer Patients Treated with Immune Checkpoint Inhibitors: A Real-World Single-Center Cohort Study.

Immune checkpoint inhibitors (ICIs) are associated with immune-related (ir) adverse events (AEs) resembling autoimmune diseases. In this retrospective cohort study of patients (pts) treated with ICIs at Oulu University Hospital from 2014-2020, we analysed the spectrum of severe irAEs and their prognostic nature, focusing on rare irAEs. Pts ( = 173) with lung cancer ( = 76, 43.9%), melanoma ( = 56, 32.4%), renal and bladder cancers ( = 34, 19.7%), head and neck cancers ( = 4, 2.3%), SCC ( = 2, 1.2%), and CRC ( = 1, 0.6%) receiving single anti-PD-(L)1 ( = 160) or combination (ICI-ICI = 9, ICI-chemotherapy = 4) therapy were included. The survival analysis focused on single anti-PD-(L)1-treated patients with melanoma, lung cancer, and renal and bladder cancers ( = 142). Grade ≥ 3 irAEs of multiple aetiology occurred in 29 patients treated with single-PD-L1 therapy (20.4%), which was associated with improved progression-free survival (PFS) (HR 0.50, CI 0.31-0.78) but not overall survival (OS) (HR 0.88, CI 0.52-1.50). Rare grade ≥ 3 events occurred in 10 (7.0%) pts with no association with PFS (HR 0.90, CI 0.42-1.94). Hence, the presence of rare grade ≥ 3 irAEs was associated with a tendency for inferior OS (HR 1.44, CI 0.66-3.11). Pts with rare grade ≥ 3 irAEs had inferior OS, possibly reflecting the delay in diagnostic workflow and the treatment of irAEs. One explanation for the high incidence of irAEs could be the Finnish population-based genetic variation affecting the immune system.