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Updated: Jul 17, 2026

Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model
Published on: February 10, 2023
Real-world risks of neurotoxicity with immune checkpoint inhibitors compared with standard chemotherapy
Alexandra Balshi1, John P Dempsey2, Yanli Zhang-James2
1Harvard Medical School, Boston, MA, USA.
Background:
Although reports of immune checkpoint inhibitor-related neurotoxicity are mounting, the relative risks of neurologic complications compared with conventional chemotherapy (also associated with neurotoxicity) remain poorly defined.
Objective:
To conduct a large, multicenter, real-world cohort study comparing neurologic adverse events among those treated with immune checkpoint inhibitors (ICIs) versus conventional (platinum-based) chemotherapy.
Methods:
We utilized data from the TriNetX research network from 2011 to 2026. We propensity-score 1:1 matched people with cancer who initiated an ICI versus conventional chemotherapy by cancer type along with age, sex, race, ethnicity, body mass index, tobacco use, and other comorbidities. Matched cohorts (n = 46,909 per cohort) were compared using risk ratios (RRs) with 95% confidence intervals (CIs).
Results:
ICIs were associated with significantly greater risks of demyelinating disease (RR 1.42, 95% CI 1.05-1.84), neuromuscular junction disorders (RR 1.43, 95% CI 1.24-1.65), aseptic meningitis (RR 1.61, 95% CI 1.28-2.02), myopathy (RR 1.52, 95% CI 1.27-1.82), Guillain-Barré syndrome (RR 1.87, 95% CI 1.14-3.08), and radiculopathy (RR 1.14, 95% CI 1.06-1.24) compared with conventional chemotherapy. The risks of myelitis (RR 1.50 95% CI 0.85-2.64) and dysautonomia (RR 0.85, 95% CI 0.71-1.01) were equivocal, while chemotherapy was associated with greater risks of neuropathy (RR 0.46, 95% CI 0.44-0.48).
Conclusion:
In this large, multicenter, real-world cohort study, increased risks of central nervous system, neuromuscular junction, and myopathic toxicities, albeit rare overall, were observed in people with malignancy treated with ICI in comparison to conventional chemotherapy.
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