Concentrations of S100B and neurofilament light chain in blood as biomarkers for checkpoint inhibitor–induced CNS inflammationResearch in context
Sara Bjursten,
Zhiyuan Zhao,
Hifaa Al Remawi,
Marie Studahl,
Ankur Pandita,
Joel Simrén,
Henrik Zetterberg,
Anna-Carin Lundell,
Anna Rudin,
Lars Ny,
Max Levin
Affiliations
Sara Bjursten
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Corresponding author. Department of Oncology, Sahlgrenska University Hospital, Blå Stråket 6, SE-413 45 Göteborg, Sweden.
Zhiyuan Zhao
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Hifaa Al Remawi
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
Marie Studahl
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden
Ankur Pandita
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Joel Simrén
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Henrik Zetterberg
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China
Anna-Carin Lundell
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Anna Rudin
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Lars Ny
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
Max Levin
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Summary: Background: Cancer treatment with immune checkpoint inhibition (ICI) can cause immune-related adverse events in the central nervous system (CNS irAE). There are no blood biomarkers to detect CNS irAE. We investigated if concentrations of S100-calcium-binding protein B (S100B) and neurofilament light chain (NfL) in blood can be used as biomarkers for CNS irAE and assessed the incidence of CNS irAE in a cohort of ICI-treated patients. Methods: In this single-centre, retrospective cohort study, we examined medical records and laboratory data of 197 consecutive patients treated with combined CTLA-4 and PD-1 inhibition (ipilimumab; ipi + nivolumab; nivo) for metastatic melanoma or renal cell carcinoma. CNS irAE was diagnosed using established criteria. Concentrations of S100B and NfL in blood were measured in patients with CNS irAE and in 84 patients without CNS irAE. Findings: Nine of 197 patients (4.6%) fulfilled criteria for CNS irAE. S100B and NfL in blood increased during CNS inflammation and normalized during immunosuppression. CNS irAE was detected with a sensitivity of 100% (S100B) and 79% (NfL) and a specificity of 89% (S100B) and 74% (NfL). Patients with CNS irAE had simultaneous increased concentration of C-reactive protein (CRP) (9/9) and alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) in blood (8/9). Interpretation: Analysis of S100B, NfL and CRP in blood facilitates the diagnosis of CNS irAE. CNS irAE may be more common than previously reported. There may be shared immune mechanisms between CNS and hepatitis irAE. Funding: Supported by funding from the Swedish Cancer Foundation, the ALF-agreement, and Jubileumsklinikens Cancerfond.
