Journal article
Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors
Journal for immunotherapy of cancer, Vol.9(7), e002890
07/19/2021
DOI: 10.1136/jitc-2021-002890
PMCID: PMC8291304
PMID: 34281989
Abstract
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.
Details
- Title: Subtitle
- Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors
- Creators
- Amanda C Guidon - Division of Neuromuscular Medicine, Department of Neurology, Massachusetts General Hospital, Boston, MA, USALeeann B Burton - Division of Neuromuscular Medicine, Department of Neurology, Massachusetts General Hospital, Boston, MA, USABart K Chwalisz - Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USAJames Hillis - Division of Neuroimmunology and Neuroinfectious Disease, Massachusetts General Hospital, Boston, Massachusetts, USATeilo H Schaller - Project Data Sphere, Cary, North Carolina, USAAnthony A Amato - Division of Neuromuscular Medicine, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USAAllison Betof Warner - Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USAPriscilla K Brastianos - Department of Medicine, Massachusetts General Hospital, Boston, MA, USATracey A Cho - Department of Neurology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAStacey L Clardy - Department of Neurology, University of Utah, Salt Lake CIty, UT, USAJustine V Cohen - Division of Oncology, Department of Medicine, University of Pennsylvania, PA, USAJorg Dietrich - Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USAMichael Dougan - Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USAChristopher T Doughty - Division of Neuromuscular Medicine, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USADivyanshu Dubey - Departments of Neurology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USAJeffrey M Gelfand - Department of Neurology, UCSF, San Francisco, California, USAJeffrey T Guptill - Division of Neuromuscular Medicine, Duke University, Durham, NC, USADouglas B Johnson - Division of Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USAVern C Juel - Division of Neuromuscular Medicine, Duke University, Durham, NC, USARobert Kadish - Department of Neurology, University of Utah, Salt Lake CIty, UT, USANoah Kolb - Division of Neuromuscular Medicine, Department of Neurology, University of Vermont, Burlington, VT, USANicole R LeBoeuf - Department of Dermatology, Center for Cutaneous Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USAJenny Linnoila - Division of Neuroimmunology and Neuroinfectious Disease, Massachusetts General Hospital, Boston, Massachusetts, USAAndrew L Mammen - Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USAMaria Martinez-Lage - Division of Neuropathology, Department of Pathology, Massachusetts General Hospital, Boston, MA, USAMeghan J Mooradian - Division of Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USAJarushka Naidoo - Upper Aerodigestive Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins University, Baltimore, MD, USATomas G Neilan - Cardio-oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USADavid A Reardon - Center for Neuro-oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USAKrista M Rubin - Division of Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USABianca D Santomasso - Department of Neurology, Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USARyan J Sullivan - Division of Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USANancy Wang - Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USAKarin Woodman - Section of Cancer Neurology, Department of Neuro-Oncology, MD Anderson Cancer Center, Houston, TX, USALeyre Zubiri - Division of Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USAWilliam C Louv - Project Data Sphere, Cary, North Carolina, USAKerry L Reynolds - Division of Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Resource Type
- Journal article
- Publication Details
- Journal for immunotherapy of cancer, Vol.9(7), e002890
- DOI
- 10.1136/jitc-2021-002890
- PMID
- 34281989
- PMCID
- PMC8291304
- eISSN
- 2051-1426
- Grant note
- name: Project Data Sphere, award: Neurologic irAE Registry with Massachusetts Genera
- Language
- English
- Date published
- 07/19/2021
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984107358702771
Metrics
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