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Abstract Details

Neurological toxicity in cancer patients treated with immune check-point inhibitor therapy
Autoimmune Neurology
S43 - Immunotherapies and Drug Trials in Autoimmune Neurological Disorders (4:58 PM-5:09 PM)
009

Immune check point inhibitor (ICI) therapies targeting cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), programmed cell death (PD-1) and its ligand PD-L1 used for cancer treatment can cause neurologic immune related adverse events (irAE). 

To characterize the neurological toxicities in cancer patients receiving immune check-point inhibitor therapy.

This is a single-center retrospective analysis of 11 patients who received ICI therapy for cancer at the National Institutes of Health (NIH) with reported neurological irAE (neuro-irAE). Informed consent was obtained. 

Eleven patients were treated with either nivolumab, pembrolizumab, durvalumab, nivolumab+ipilimumab, or nivolumab+CEA-MUC-1-TRICOM vaccine CV301. All patients had metastatic genitourinary cancers or non-small cell lung cancer. The median time to onset of neuro-irAE was 4.4 months (range – 0.5-12).  One patient on nivolumab +ipilimumab combination developed autoimmune limbic encephalitis on MRI with lymphocytic pleocytosis and progressive 6thcranial nerve palsies. Another patient on nivolumab had aseptic meningitis with mild leptomeningeal enhancement on MRI, lymphocytic pleocytosis and increased protein. One patient on nivolumab+ CV301 developed multifocal embolic infarcts. One patient on durvalumab plus olaparib had optic neuritis. Treatment with immune checkpoint inhibitor was held in five patients and continued in six patients. Using CTCAE v4.03 criteria, all neuro-irAEs were grade 3 or below, with 5/16 grade 3, 8/16 grade 2, and 2/16 grade 1. 13/16 neuro-irAEs were definitely, probably or possibly related to study drug, with only 3/16 events being unlikely to be related to ICI therapy. 

9/11 patients had immune-mediated neurological AEs related to study drug. 7/16 of the neurologic irAEs were definitely related to study drug. In this series, 5/7 definitely related irAEs resulted from combination ICI therapy. In summary, immune check point modulation has the potential to cause a variety of serious autoimmune neurological adverse events

Authors/Disclosures
Lauren Reoma, MD, FAAN (NIH/NINDS)
PRESENTER
Dr. Reoma has received research support from NIH. Dr. Reoma has a non-compensated relationship as a Vice Chair with AAN Experimental Neurotherapeutics Section that is relevant to AAN interests or activities. Dr. Reoma has a non-compensated relationship as a Federal Employee with NINDS/NIH that is relevant to AAN interests or activities. Dr. Reoma has a non-compensated relationship as a Member with ASENT Program Committee that is relevant to AAN interests or activities.
Ram N. Narayan, MD (Barrow Neurological Institute) Dr. Narayan has nothing to disclose.
No disclosure on file
Aashrai S. Gudlavalleti, MBBS (Ohio Health) Dr. Gudlavalleti has nothing to disclose.
Bryan Smith, MD (NIH) Dr. Smith has nothing to disclose.
Matthew Schindler, MD, PhD (Univeristy of Pennsylvania) Dr. Schindler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapuetics. Dr. Schindler has received personal compensation in the range of $5,000-$9,999 for serving as a 好色先生al Presenter with Annenberg Center.
Daniel Reich, MD, PhD (National Institutes of Health, Neuroimmunology Branch, NINDS) Dr. Reich has received research support from NIH. The institution of Dr. Reich has received research support from Adelson Medical Research Foundation. The institution of Dr. Reich has received research support from Sanofi. The institution of Dr. Reich has received research support from Abata Therapeutics. The institution of Dr. Reich has received research support from National Multiple Sclerosis Society. Dr. Reich has received intellectual property interests from a discovery or technology relating to health care. Dr. Reich has received personal compensation in the range of $5,000-$9,999 for serving as a CME Faculty with PeerView. Dr. Reich has received personal compensation in the range of $5,000-$9,999 for serving as a CME Faculty with Integrity. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Letters and Sciences. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Academic CME. Dr. Reich has a non-compensated relationship as a Advisor with Sanofi that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Board of Directors with ACTRIMS that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Abata Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with University of Basel RC2NB that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Multiple Sclerosis Society of Canada that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Tuscan Doctorate in Neuroscience that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Editorial Board with Multiple Sclerosis Journal that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Biohaven that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Sana that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Merck KGaA EMD Serono that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Bristol-Meyers Squibb that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with ChemoCentryx that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Hyperfine that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Imaginab that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Perceptive that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Annexon that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Philips that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Siemens that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Novartis that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Calico Life Sciences that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Cognito Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Sudo that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Allumis that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with BioCentury that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Regeneron that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Eli Lilly that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with SetPoint that is relevant to AAN interests or activities.
No disclosure on file
No disclosure on file
Arun B. Rajan, MD (Prime Medical Associates, LLC) No disclosure on file
No disclosure on file
Omar Khan, MD, FAAN Dr. Khan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Khan has received personal compensation in the range of $100,000-$499,999 for serving as a Director of Epilepsy Center with Veterans Affairs. An immediate family member of Dr. Khan has received personal compensation in the range of $100,000-$499,999 for serving as a Clinical Reviewer with FDA.
Avindra Nath, MD, MBBS, FAAN (National Institutes of Health) Dr. Nath has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Nath has received research support from National Institutes of Health. The institution of Dr. Nath has received research support from ALS Association. Dr. Nath has received intellectual property interests from a discovery or technology relating to health care.