Immune checkpoint inhibitor-related neurotoxicity: Incidence and management. A systematic review and meta-analysis Journal Article

  


Authors: Nielsen, D. L.; Juhl, C. B.; Chen, I. M.; Wang, Y.; Nielsen, O. H.; Santomasso, B. D.
Article Title: Immune checkpoint inhibitor-related neurotoxicity: Incidence and management. A systematic review and meta-analysis
Abstract: Background: Immune checkpoint inhibitors (ICIs) have improved outcomes for various malignancies. However, serious immune-related adverse events (irAEs), including neurologic complications (NAEs), may occur. The aim of this study was to examine the incidence and spectrum of NAEs and evaluate management strategies for reducing their impact. Methods: Two studies were conducted: 1) A meta-analysis of phase I-IV clinical trials involving adults with malignancies treated with ICIs, either as monotherapy, in combination with other ICIs, or with chemotherapy. The primary outcome was the incidence of (ir)NAEs, summarized using a meta-analysis with a random-effects model. 2) A systematic review of the literature addressing the clinical manifestations and treatment of irNAEs. Results: The meta-analysis included 657 unique trials with 91,340 participants. For all ICIs, the incidence of all-grade NAEs was 0.24% (95% CI, 0.15–0.32%). Cerebral events, cerebrovascular accidents, were increased post-treatment and accounted for 54% of all grade-5 events in clinical trials. Among 991 reported irNAE cases, 77% of patients improved with treatment; however, 42% experienced unresolved sequelae and the overall mortality rate was 17.1%. Among patients with overlapping myasthenia gravis, myositis, and myocarditis (“Triple M”), the mortality reached 38%; primarily due respiratory failure (50%) or cardiotoxicity (41%). Conclusions: Although the incidence of ICI-related NAEs is low such side effects may lead to severe morbidity and mortality. In patients with Triple M syndrome intensive respiratory function monitoring and support are essential parameters to improve the outcome. PROSPERO Protocol # CRD42023463750. © 2025 Elsevier B.V., All rights reserved.
Keywords: cancer chemotherapy; clinical feature; review; monotherapy; neurotoxicity; ipilimumab; incidence; confidence interval; patient care; clinical study; systematic review; cardiotoxicity; comorbidity; cytotoxic t lymphocyte antigen 4; encephalitis; myasthenia gravis; neurological complication; meningitis; meta analysis; cranial neuropathy; cerebrovascular accident; neuromuscular disease; respiratory failure; meta-analysis; programmed death 1 ligand 1; phase 2 clinical trial (topic); phase 3 clinical trial (topic); phase 1 clinical trial (topic); myositis; myelitis; mortality rate; myocarditis; case reports; immune checkpoint inhibitor; phase 4 clinical trial (topic); nivolumab; human; pembrolizumab; durvalumab; atezolizumab; avelumab; malignant neoplasm; neurologic toxicity; cemiplimab; myasthenia; polyradiculoneuropathy; dostarlimab
Journal Title: Cancer Treatment Reviews
Volume: 140
ISSN: 0305-7372
Publisher: Elsevier Inc.  
Date Published: 2025-01-01
Start Page: 103011
Language: English
DOI: 10.1016/j.ctrv.2025.103011
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-105012950304&doi=10.1016%2Fj.ctrv.2025.103011&partnerID=40&md5=33304dd240e1ffb32f2b5fb62d46101c
Notes: Review -- Source: Scopus
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