PT - JOURNAL ARTICLE AU - Amanda C Guidon AU - Leeann B Burton AU - Bart K Chwalisz AU - James Hillis AU - Teilo H Schaller AU - Anthony A Amato AU - Allison Betof Warner AU - Priscilla K Brastianos AU - Tracey A Cho AU - Stacey L Clardy AU - Justine V Cohen AU - Jorg Dietrich AU - Michael Dougan AU - Christopher T Doughty AU - Divyanshu Dubey AU - Jeffrey M Gelfand AU - Jeffrey T Guptill AU - Douglas B Johnson AU - Vern C Juel AU - Robert Kadish AU - Noah Kolb AU - Nicole R LeBoeuf AU - Jenny Linnoila AU - Andrew L Mammen AU - Maria Martinez-Lage AU - Meghan J Mooradian AU - Jarushka Naidoo AU - Tomas G Neilan AU - David A Reardon AU - Krista M Rubin AU - Bianca D Santomasso AU - Ryan J Sullivan AU - Nancy Wang AU - Karin Woodman AU - Leyre Zubiri AU - William C Louv AU - Kerry L Reynolds TI - Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors AID - 10.1136/jitc-2021-002890 DP - 2021 Jul 01 TA - Journal for ImmunoTherapy of Cancer PG - e002890 VI - 9 IP - 7 4099 - http://jitc.bmj.com/content/9/7/e002890.short 4100 - http://jitc.bmj.com/content/9/7/e002890.full SO - J Immunother Cancer2021 Jul 01; 9 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.