University of Oulu

Kuusisalo S, Koivunen JP, Iivanainen S. 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. Cancers. 2022; 14(9):2276.

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

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Author: Kuusisalo, Saara1; Koivunen, Jussi P.1; Iivanainen, Sanna1
Organizations: 1Department of Oncology and Radiotherapy, Oulu University Hospital and MRC Oulu, 90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2022
Publish Date: 2022-09-07


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 (n = 173) with lung cancer (n = 76, 43.9%), melanoma (n = 56, 32.4%), renal and bladder cancers (n = 34, 19.7%), head and neck cancers (n = 4, 2.3%), SCC (n = 2, 1.2%), and CRC (n = 1, 0.6%) receiving single anti-PD-(L)1 (n = 160) or combination (ICI-ICI n = 9, ICI-chemotherapy n = 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 (n = 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.

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Series: Cancers
ISSN: 2072-6694
ISSN-E: 2072-6694
ISSN-L: 2072-6694
Volume: 14
Issue: 9
Article number: 2276
DOI: 10.3390/cancers14092276
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: Oulu University, the Emil Aaltonen Foundation, the Finnish Medical Foundation, and the Finnish Cancer Society funded the study.
Copyright information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (