Open Access

ARTICLE

Elevated C-Reactive Protein as a Potential Biomarker for Neurological Adverse Events in Immune Checkpoint Inhibitor Therapy: A Prospective Cohort Study

Laura Duzzi^1,#,*, Nora Möhn^1,#, Emily Narten¹, Janin Thomas¹, Susann Mahjoub¹, Lea Grote-Levi¹, Konstantin Jendretzky¹, Sandra Nay¹, Felix Konen¹, Jonas Wiegmann², Gernot Beutel², Tabea Fröhlich², Benjamin-Alexander Bollmann³, Thomas Wirth⁴, Imke von Wasielewski⁵, Florian H. Heidel², Ralf Gutzmer^5,6, Thomas Skripuletz^1,§, Philipp Ivanyi^2,§, the ICOG (Immune Cooperative Oncology Group)-Investigators⁷

1 Department of Neurology, Hannover Medical School, Hannover, Germany
2 Department of Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
3 Department of Pneumology, Hannover Medical School, Hannover, Germany
4 Department of Gastroenterology, Hannover Medical School, Hannover, Germany
5 Skin-Cancer-Center, Department of Dermatology, Allergology, and Venereology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, Germany
6 Department of Dermatology, Johannes Wesling Medical Center, Ruhr University Bochum, Minden, Germany
7 Study Group, Comprehensive Cancer Center Niedersachsen (CCCN), Niedersachsen, Germany

* Corresponding Author: Laura Duzzi. Email:
# These authors contributed equally as first authors to this work
§ These authors contributed equally as senior authors to this work

(This article belongs to the Special Issue: Advances in Cancer Immunotherapy)

Oncology Research 2026, 34(5), 17 https://doi.org/10.32604/or.2026.074095

Received 01 October 2025; Accepted 09 February 2026; Issue published 22 April 2026

Abstract

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.

---

Keywords

---

Supplementary Material

Supplementary Material File

---