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Elevated C-Reactive Protein as a Potential Biomarker for Neurological Adverse Events in Immune Checkpoint Inhibitor
Laura Duzzi1, Nora Möhn1, Emily Narten1
1Department of Neurology, Hannover Medical School, Hannover, Germany.
Objectives:
Since 2011, immune checkpoint inhibitors (ICI) have transformed the treatment of various cancers. However, our understanding of the autoimmune adverse events, particularly those affecting the nervous system, remains limited. These adverse events can cause significant disability or even death, yet there are currently no established guidelines or biomarkers to aid diagnosis and treatment. With this study, we aim to gain a deeper understanding of neurological adverse events and investigate potential predictive biomarkers.
Methods:
Between 19 December 2019 and 21 August 2021, 150 out of 543 ICI-treated cancer patients were eligible for our prospective monocentric cohort study. Neurological assessments, clinical scores and the severity of side effects were analysed. Blood samples were taken before, during and after therapy. Patients with neurological AEs (the nAE group) and those without (the non-nAE group) were compared to identify potential predictive markers.
Results:
Of the 150 patients, 55 (36.7%) experienced nAE of any kind or severity, ranging from non-specific neurological symptoms to severe events. Severe nAE (Grade ≥ 3) was observed in 3.3% of patients and included cases of encephalitis and cerebral vasculitis. Regarding potential biomarkers, an increase in C-reactive protein (CRP) within the first 3-4 weeks was statistically associated with an increased likelihood of nAE in this study. As for patient- and treatment-related parameters, concurrent chemotherapy was found to be significantly associated with the occurrence of nAE.
Conclusions:
This study observed a relatively high rate of nAE under ICI therapy, partly due to the intentionally broad case definition. CRP elevation emerged as a potential predictive biomarker, warranting further investigation. However, other statistically significant markers did not consistently demonstrate clinical relevance.
Insights
Immune checkpoint inhibitors (ICI) can cause neurological side effects in cancer patients. An increase in C-reactive protein (CRP) during treatment may predict these adverse events, suggesting a potential biomarker for early detection.
Area of Science:
- Oncology
- Neuroimmunology
- Cancer Therapeutics
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment since 2011.
- Neurological autoimmune adverse events (nAEs) from ICIs are poorly understood, lacking diagnostic and treatment guidelines.
- These nAEs can lead to severe disability or death.
Purpose of the Study:
- To investigate the incidence and characteristics of neurological adverse events in cancer patients treated with ICIs.
- To identify potential predictive biomarkers for these nAEs.
- To explore patient and treatment-related factors associated with nAE occurrence.
Main Methods:
- A prospective monocentric cohort study included 150 cancer patients treated with ICIs between December 2019 and August 2021.
- Neurological assessments, clinical scores, and side effect severity were analyzed.
- Blood samples were collected throughout therapy, and patients with and without nAEs were compared for potential biomarkers.
Main Results:
- 55 out of 150 patients (36.7%) experienced nAEs, with 3.3% experiencing severe events (Grade ≥ 3), including encephalitis and cerebral vasculitis.
- Elevated C-reactive protein (CRP) within the first 3-4 weeks of therapy was statistically associated with an increased likelihood of nAEs.
- Concurrent chemotherapy was significantly associated with the occurrence of nAEs.
Conclusions:
- The study identified a notable rate of nAEs in ICI-treated patients, influenced by a broad case definition.
- CRP elevation shows promise as a predictive biomarker for nAEs, meriting further research.
- While other markers were statistically significant, they lacked consistent clinical relevance.
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