RT Journal Article
SR Electronic
T1 Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e002890
DO 10.1136/jitc-2021-002890
VO 9
IS 7
A1 Amanda C Guidon
A1 Leeann B Burton
A1 Bart K Chwalisz
A1 James Hillis
A1 Teilo H Schaller
A1 Anthony A Amato
A1 Allison Betof Warner
A1 Priscilla K Brastianos
A1 Tracey A Cho
A1 Stacey L Clardy
A1 Justine V Cohen
A1 Jorg Dietrich
A1 Michael Dougan
A1 Christopher T Doughty
A1 Divyanshu Dubey
A1 Jeffrey M Gelfand
A1 Jeffrey T Guptill
A1 Douglas B Johnson
A1 Vern C Juel
A1 Robert Kadish
A1 Noah Kolb
A1 Nicole R LeBoeuf
A1 Jenny Linnoila
A1 Andrew L Mammen
A1 Maria Martinez-Lage
A1 Meghan J Mooradian
A1 Jarushka Naidoo
A1 Tomas G Neilan
A1 David A Reardon
A1 Krista M Rubin
A1 Bianca D Santomasso
A1 Ryan J Sullivan
A1 Nancy Wang
A1 Karin Woodman
A1 Leyre Zubiri
A1 William C Louv
A1 Kerry L Reynolds
YR 2021
UL http://jitc.bmj.com/content/9/7/e002890.abstract
AB Expanding the US Food and Drug Administration–approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%–12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.All data relevant to the study are included in the article.