The Lancet Regional Health. Europe (Sep 2024)
Diagnostic and prognostic biomarkers in immune checkpoint inhibitor-related encephalitis: a retrospective cohort studyResearch in context
- Antonio Farina,
- Macarena Villagrán-García,
- Anthony Fourier,
- Anne-Laurie Pinto,
- Fatima Chorfa,
- Noémie Timestit,
- Tifanie Alberto,
- Jérôme Aupy,
- Marie Benaiteau,
- Cristina Birzu,
- Lucia Campetella,
- François Cotton,
- Stéphane Dalle,
- Clara Fontaine Delaruelle,
- Pauline Dumez,
- Rafaele Germi,
- Marion Le Maréchal,
- Denis Maillet,
- Romain Marignier,
- Antoine Pegat,
- Dimitri Psimaras,
- Marie Rafiq,
- Géraldine Picard,
- Virginie Desestret,
- Isabelle Quadrio,
- Jérôme Honnorat,
- Bastien Joubert
Affiliations
- Antonio Farina
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Macarena Villagrán-García
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Anthony Fourier
- Lyon Neuroscience Research Center (CRNL), Université de Lyon, CNRS, INSERM, Lyon, France
- Anne-Laurie Pinto
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Fatima Chorfa
- Service de Biostatistique et Bioinformatique, Pôle Santé Publique, Hospices Civils de Lyon, Lyon, France
- Noémie Timestit
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Tifanie Alberto
- Department of Neurology, CRC SEP, Centre Hospitalier of Lille, Lille, France
- Jérôme Aupy
- Department of Clinical Neurosciences, Centre Hospitalier of Bordeaux, Bordeaux, France; CNRS, IMN, UMR 5293, University of Bordeaux, Bordeaux, France
- Marie Benaiteau
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Cristina Birzu
- AP-HP, Hospital Group Pitié-Salpêtrière, Neuro-oncology Department Paris, France; Inserm U1127, CNRS, Paris Brain Institute, Institut du Cerveau (ICM), Paris, France
- Lucia Campetella
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- François Cotton
- Radiology Department, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France
- Stéphane Dalle
- Deparment of Dermatology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France; ImmuCare, Institute of Cancerology, Hospices Civils de Lyon, Lyon 69002, France
- Clara Fontaine Delaruelle
- ImmuCare, Institute of Cancerology, Hospices Civils de Lyon, Lyon 69002, France; Department of Pneumology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France
- Pauline Dumez
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Rafaele Germi
- Virology, Grenoble-Alpes University Hospital, Grenoble, France
- Marion Le Maréchal
- Infectious Disease Unit, Grenoble-Alpes University Hospital, Grenoble, France
- Denis Maillet
- ImmuCare, Institute of Cancerology, Hospices Civils de Lyon, Lyon 69002, France; Department of Medical Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France
- Romain Marignier
- Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Hospices Civils de Lyon, Lyon, France
- Antoine Pegat
- Service ENMG et Pathologies Neuromusculaires, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Est, Lyon, France
- Dimitri Psimaras
- AP-HP, Hospital Group Pitié-Salpêtrière, Neuro-oncology Department Paris, France; Inserm U1127, CNRS, Paris Brain Institute, Institut du Cerveau (ICM), Paris, France
- Marie Rafiq
- Department of Cognitive Neurology, Epilepsy and Movement Disorders, Toulouse Purpan University Hospital Center, Toulouse, France
- Géraldine Picard
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Virginie Desestret
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Isabelle Quadrio
- Lyon Neuroscience Research Center (CRNL), Université de Lyon, CNRS, INSERM, Lyon, France
- Jérôme Honnorat
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France
- Bastien Joubert
- French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France; MeLiS-UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France; ImmuCare, Institute of Cancerology, Hospices Civils de Lyon, Lyon 69002, France; Corresponding author. French Reference Centre for Paraneoplastic Neurological Syndromes, Neurological Hospital, 59 Boulevard Pinel, Bron Cedex 69677, France.
- Journal volume & issue
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Vol. 44
p. 101011
Abstract
Summary: Background: Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking. We aimed to comprehensively characterise ICI-encephalitis and identify diagnostic biomarkers and outcome predictors. Methods: This retrospective observational study included all patients with ICI-encephalitis studied in the French Reference Centre on Paraneoplastic Neurological Syndromes (PNS) and Autoimmune Encephalitis (2015–2023). ICI encephalitis was considered definite in case of inflammatory findings at paraclinical tests and/or well-characterised neural antibodies. Predictors of immune-related adverse event (irAE) treatment response, defined as a Common Terminology Criteria for Adverse Events v5.0 grade 273.5 pg/mL, sensitivity 81%, specificity 88%, AUC 0.87, 95% CI [0.76; 0.98]) and irAE treatment responders (n = 10) from non-responders (n = 17, optimal cut-off >645 pg/mL, sensitivity 90%, specificity 65%; AUC 0.75, 95% CI [0.55; 0.94]). Interpretation: ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low irAE treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations. Funding: Agence Nationale de la Recherche.
