Abstract Details

Title Immune checkpoint inhibitor related neurologic adverse events: clinical spectrum, management and outcomes

Topic Autoimmune Neurology

Presentation(s) S21 - Autoimmune Neurology: Novel Diagnostic and Predictive Biomarkers and Immunopathologic Mechanisms of Disease (3:52 PM-4:03 PM)

Poster/Presentation
Number 003

Objective To describe the clinical spectrum, management and clinical outcomes of neurologic immune-related adverse events (IrAEs) in a large cohort of patients who received immune checkpoint inhibitors (ICIs).

Background Expanding use of ICIs underscores the importance of accurate diagnosis and prompt management of neurologic IrAEs. Because neurologic irAEs may present atypically with overlap, and optimal management is unknown, comprehensive phenotypic characterization and long-term outcome data are needed.

Design/Methods Patients who received an ICI at Massachusetts General Hospital between 06/01/2011 and 12/31/2017 were identified. The instituitional-database-registry was utilized to search for relevant diagnostic-codes and/or diagnostic evaluations. We reviewed medical records of the screened cases for clinical data. Change in modified Rankin score ≥1 was considered as a favorable outcome.

Results From 2011 to 2017, 1851 patients received ICIs at our institution. Twenty-eight (1.5%) patients had grade 3 (limit self-care activities of daily living) or 4 (life threatening and need urgent intervention) neurological IrAEs. Underlying malignancies included melanoma (n=21), adenocarcinoma (n=5), renal cell carcinoma (n=1) and Hodgkin’s lymphoma (n=1). The rate of neurological IrAEs was significantly higher with use of cytotoxic-T-lymphocyte-antigen-4 inhibitors (anti-CTLA4) alone (2.8%) or in combination with programmed-death-1 inhibitors (anti-PD1) (2.7%) compared to anti-PD1 monotherapy (0.8%, p<0.05). Nine patients developed immune-mediated CNS involvement (3 with co-existing immune-mediated neuropathies, and one with myositis). Immune-mediated neuropathies and myositis and/or neuromuscular junction disorders were diagnosed in 13 and 10 patients, respectively. Most neurologic IrAEs (68%) occurred within the first 1-4 ICI cycles. Administration of oral/intravenous corticosteroids was associated with favorable outcome (76% vs 24%, p<0.05). Seven patients had recurrence of neurological deficits. Recurrence of neurologic symptoms was associated with retreatment with ICIs (86% vs 14%, p<0.01).

Conclusions Neurological irAEs are rare but potentially severe complications of ICIs. Recognition of their wide and overlapping phenotypic spectrum, distinct clinical characteristics and prompt management with corticosteroids may lead to favorable outcomes.

Authors/Disclosures
Divyanshu Dubey, MD, FAAN (Mayo Clinic) PRESENTER	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
William S. David, MD, PhD, FAAN (EMG /Neuromuscular Unit)	Dr. David has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Dysimmune Disorders foundation. Dr. David has received publishing royalties from a publication relating to health care.
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Amanda C. Guidon, MD, MPH (Massachusetts General Hospital)	An immediate family member of Dr. Guidon has received personal compensation for serving as an employee of GE Healthcare. Dr. Guidon has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Guidon has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN - Continuum. The institution of Dr. Guidon has received research support from NINDS. Dr. Guidon has received publishing royalties from a publication relating to health care. Dr. Guidon has a non-compensated relationship as a Committee Member with Myasthenia Gravis Foundation of America that is relevant to AAN interests or activities. Dr. Guidon has a non-compensated relationship as a Executive Committee Member with Neuromuscular Study Group that is relevant to AAN interests or activities.

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