Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct 1:228:115707.
doi: 10.1016/j.ejca.2025.115707. Epub 2025 Aug 9.

Neurological adverse events of ICI therapy: A ten-year comprehensive management from a multidisciplinary team

Anna Maria Di Giacomo  1 , Sabina Bartalini  2 , Vincenzo D'Alonzo  3 , Alfonso Cerase  4 , Serena Cutarella  3 , Giulia Rossi  5 , Elena Simonetti  3 , Monica Valente  5 , Matteo Ravara  3 , Maura Colucci  3 , Giulia Gibilisco  3 , Laura Insana  6 , Silvia Bocci  7 , Valentina Croce  3 , Tommaso Sani  3 , Eleonora Carbonari  3 , Alessia Covre  8 , Fabio Giannini  2 , Nila Volpi  2 , Federica Ginanneschi  2 , Michele Maio  9
Affiliations
Free article

Neurological adverse events of ICI therapy: A ten-year comprehensive management from a multidisciplinary team

Anna Maria Di Giacomo et al. Eur J Cancer. .
Free article

Abstract

Background: The unique mechanism of action of immune checkpoint inhibitors (ICI) can lead to auto-inflammatory events, potentially involving any organ. Among those, different rare immune related adverse events (irAEs) have also been identified, with Neurological irAEs (NirAEs) accounting for 1-5 %. In this scenario, we here report the 10-year experience of the multidisciplinary team at the University Hospital of Siena, Italy, in the diagnosis and clinical management of NirAEs.

Methods: A case series of ICI-treated patients with clinical suspect of Nir-AEs were evaluated by an experienced neurologist team. Neurological specific antibodies were tested in central/peripheral toxicities. In case of suspicious of CNS NirAEs, lumbar puncture was utilized to exclude infectious/paraneoplastic causes. In patients with signs and symptoms suggestive for myositis, a diagnostic muscular biopsy was performed.

Results: From January 2012 to December 2022, 1328 patients with solid tumors were treated with ICI, and 24 (1,8 %) were diagnosed with NirAEs: peripheral, central, or both in 20, 1, and 3 cases respectively. The most representative neurotoxicity was muscular/neuromuscular junction involvement. Histological examination of muscle biopsies depicted two main pathological patterns: highly inflammatory or necrotizing. NirAEs were Grade (G) 1-2 (11), G3-4 (10), G5 (3) and were treated with steroids, immunoglobulins and/or plasma exchange. Treatment led to complete or partial recovery of NirAEs in 11 (46 %) and 10 patients (42 %), respectively. In 3 cases NirAEs progressively worsened and patients died thereafter.

Conclusions: Our long-term experience indicates that a multidisciplinary approach avoids worsening of NirAEs leading to clinical recovery in the large majority of ICI-treated patients.

Keywords: Encephalitis; Guillain-Barre syndrome; Immune-checkpoint inhibitors; Myasthenia gravis; Myositis; Neurotoxicity.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AMDG has served as a consultant and/or advisor to Incyte, Pierre Fabre, Glaxo Smith Kline, Bristol-Myers Squibb, Sunpharma, Immunocore, Merck Sharp Dohme, and Sanofi and has received compensated educational activities from Bristol Myers Squibb, Merck Sharp Dohme, Sunpharma, Pierre Fabre and Sanofi; MM has served as a consultant and/or advisor to Roche, Bristol-Myers Squibb, Merck Sharp Dohme, Incyte, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, Glaxo Smith Kline, Sciclone, Sanofi, Alfasigma, and Merck Serono; and own shares in Epigen Therapeutics, Srl. MM has served as consultant and/or advisor to Roche, Bristol Myers Squibb, Merck Sharp Dohme, Incyte, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, Glaxo Smith Kline, Sciclone, Sano, Alfasigma, and Merck Serono; and own shares in Theravance and Epigen Therapeutics, Srl. MV has served as a consultant e/o advisor to Novartis. SB, VD, AC, SC, GR, ES, MR, MC, GG, LI, SB, VC, TS, EC, FG, NV, AC and FG have no conflicts of interest to declare for this work paper.

Substances

LinkOut - more resources