Evidence map›Paper›PMID 39831665›Full record

ArticleInternational journal of cancer2025

Increased serum NfL and GFAP levels indicate different subtypes of neurologic immune-related adverse events during treatment with immune checkpoint inhibitors.

Christina Schmitt, Katharina J Müller, Steffen Tiedt, Nora Kramer, Isabel Manger, Samuel Knauss, Leonie Müller-Jensen, Petra Huehnchen, Wolfgang Boehmerle, Florian Schöberl and 2 more

Abstract readClinical StudyMulticenter Study
In one paragraph

Article in International journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Neuroglial markers of damage in autoimmune neurology.Therapeutic advances in neurological disorders · 2026
    Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Christina SchmittDepartment of Dermatology and Allergy, LMU University Hospital, Munich, Germany.ORCID 0000-0001-9592-2347
Katharina J MüllerDepartment of Neurology, LMU University Hospital, Munich, Germany.
Steffen TiedtInstitute for Dementia and Stroke Research, LMU University Hospital, Munich, Germany.
Nora KramerDepartment of Dermatology and Allergy, LMU University Hospital, Munich, Germany.
Isabel MangerDepartment of Dermatology and Allergy, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Samuel KnaussDepartment of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Leonie Müller-JensenDepartment of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Petra HuehnchenDepartment of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Wolfgang BoehmerleDepartment of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Florian SchöberlDepartment of Neurology, LMU University Hospital, Munich, Germany.
Lucie HeinzerlingDepartment of Dermatology and Allergy, LMU University Hospital, Munich, Germany.
Louisa von BaumgartenDepartment of Neurosurgery, LMU University Hospital, Munich, Germany.

Funding

Bavarian Center for Cancer Research (BZKF)Berlin Institute of Health SPARK programBristol-Myers SquibbBruno-and Helene Joester foundationBundesministerium für Bildung und Forschung 01ZX1905EDeutsche Forschungsgemeinschaft SFB-TRR 338/1 2021-452881907
6 · The paper itself

Abstract

Neurologic immune-related adverse events (nirAEs) represent rare, yet severe side effects associated with immune checkpoint inhibitor (ICI) therapy. Given the absence of established diagnostic biomarkers for nirAEs, we aimed to evaluate the diagnostic utility of serum Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP). Fifty-three patients were included at three comprehensive cancer centers, of these 20 patients with manifest nirAEs and 11 patients with irHypophysitis. Controls included patients without any irAE (n = 8) and other irAEs (n = 14). Using a single-molecule enzyme-linked immunosorbent assay (Simoa), serum levels were measured prior to, during and after the manifestation of (n)irAEs in 80 samples. Symptom severity of the (n)irAEs was graded according to the Common Criteria for Adverse Events (CTCAE) version 5.0. Serum NfL levels were significantly higher in the nirAE group (n = 20) compared to irHypophysitis (n = 11; p = .0025) and controls (n = 22; p = .0384). Subgroup analysis demonstrated a significant elevation of NfL in nirAEs of the peripheral nerves (PNirAE) in contrast to neuromuscular syndromes (NMirAE) (p = .0260). GFAP levels were highest in patients with nirAE affecting the central nervous system (CNSirAE) compared to PNirAE and NMirAE (p = .0064). Symptom severity of nirAEs was associated with increased levels of NfL and GFAP (p = .0069, .0092). Individuals with elevated NfL levels exhibited less favorable outcomes of the (n)irAEs (p = .0199). Measurement of NfL and GFAP may be helpful for the differentiation of the broad spectrum of nirAEs and may serve as an indicator of symptom severity. Further investigation is needed to evaluate their potential as diagnostic and prognostic biomarkers.

Indexed as

Glial Fibrillary Acidic ProteinImmune Checkpoint InhibitorsNeoplasmsNervous System DiseasesNeurofilament ProteinsAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedGFAP protein, humanGlial Fibrillary Acidic ProteinImmune Checkpoint Inhibitorsneurofilament protein LNeurofilament Proteinsbiomarkerimmune checkpoint inhibitorsmelanomaneurological immune‐related adverse eventsneurotoxicity

Identifiers

PMID39831665
PMCPMC11924309

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.