Background: Traditionally, cytotoxic chemotherapy dominated cancer treatment, but in recent years, immunotherapies, mainly immune checkpoint inhibitors (ICIs), have revolutionized cancer therapy by enhancing T-cell responses. Despite their efficacy, ICIs can induce toxicities affecting various organs, including the nervous system. Although rare, neurological complications of ICIs can be severe, contributing significantly to treatment-related mortality. Atezolizumab, targeting programmed death ligand 1, is approved for various cancers, with a side effect profile akin to other ICIs. While neurological adverse events with atezolizumab are less frequent, serious cases have been documented. Diagnosing these events is challenging due to atypical symptoms and limited experience in managing them. This review aimed to characterize the clinical presentation of atezolizumab-induced neurotoxicity, including neurological symptoms, diagnostic approaches, and treatment outcomes.

Methods: A Medline search conducted on atezolizumab-induced neurotoxicity using PubMed, ScienceDirect, and Google Scholar databases until March 15, 2024.

The search strategy encompassed MeSH terms and free-text words, incorporating terms such as atezolizumab, PD-L1, neurotoxicity, and various neurological adverse events. Inclusion criteria comprised English language publications, all age groups, randomized clinical trials, observational studies, systematic reviews, case reports, and case series.

Results: Of the 56 citations identified, 39 (representing 45 patients’ cases) were included. Atezolizumab-induced neurotoxicity exhibits various clinical presentations, with grades 1-2 neurotoxicities being common and typically nonspecific, while grades 3-4 syndromes are less frequent and more severe. These adverse events were documented across various cancer types, with patients who had a median age of 58 years. Symptoms typically appeared after the first cycle of atezolizumab therapy, with a median onset of two weeks after the last dose. Management typically involved steroid therapy, with a few patients requiring additional interventions such as intravenous immunoglobulin or plasmapheresis. Symptoms usually resolved within a median of 10 days after atezolizumab cessation, with partial or complete recovery in most cases. Fatal outcomes were observed in 10 cases, although causality was not definitively established in all instances. 

Conclusions: Atezolizumab-induced neurotoxicity is challenging to recognize due to widely varying symptoms, emphasizing the need for a thorough safety assessment to determine the incidence and patient risk profiles.

Continued research into this adverse event is crucial for understanding patient susceptibility and developing effective management strategies.

Immune related adverse events, Central nervous system, Atezolizumab, Immune checkpoint inhibitors, Neurological complications, Encephalitis, Neuropathy, Coma, Seizures