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

Journal volume & issue
Vol. 44
p. 101011

Abstract

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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.

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