Abstract Details

Title Incidence and Outcome of Neurologic Immune-related Adverse Events Associated with Immune Checkpoint Inhibitors in Patients with Melanoma

Topic Autoimmune Neurology

Presentation(s) S38 - Autoimmune Neurology: Peripheral Autoimmunity, Paraneoplastic Disease, Checkpoint Inhibitors, and Neurosarcoidosis (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background N-irAEs reportedly occur in up to 8% of patients treated with immune-checkpoints inhibitors (ICI), they may be severe and life-threatening and can lead to cancer treatment interruption.

Objective To Investigate and characterize Neurological Immune Related Adverse Events (n-irAEs) following cancer immunotherapy as well as age and non-age-related variables impacting survival and treatment outcomes.

Design/Methods We conducted a retrospective analysis of advanced melanoma patients treated with ICI at our institute over a 7-years period. We focused on age-related frequency and severity of n-irAE, ICI interruption, treatment and management, safety of ICI reintroduction, and n-irAE’s impact on overall survival.

Results ICI was administered to 937 patients. One or more IrAEs occurred in 73.5% (n=689) of them. Neurological-irAE developed in 8% (n=76), with median age of 66 in females and 68 in males. Median interval from initial ICI treatment to n-irAE development was 48 days across age groups with fewer irAEs occurred in patients older than 70 years (median: 3 events, p=0.04, CI:2.5-4.7). Grade ≥ 3 toxicity manifested in 35.5% of patients. Most common n-irAE phenotypes were myositis (n=34 44.7%), encephalitis (n=8 10.5%), and neuropathy (n=8 10.5%). N-irAE resulted in hospitalization in 40% of patients, and steroids treatment in 46%, median of 4 days from n-irAE diagnosis to steroids treatment initiation. Nine patients needed second-line immunosuppressive treatment. No additional n-irAE was caused by rechallenge in the majority of patients (71%). Developing n-irAE (HR=0.4, 95% CI:0.32,0.77) or any irAE (HR=0.7195% CI:0.56,0.88) was associated with longer survival.

Conclusions Neurological-irAEs occur relatively frequently in patients treated with ICI (8% of our cohort). Older age was not associated with its development or severity, unlike non-neurological-irAE which occurred less frequently in the elderly. No life-threatening AEs occurred following rechallenge. IrAE development was clearly associated with longer overall survival, this association was even stronger with neurological-irAEs.

Authors/Disclosures
Shahar Shelly, MD (Rambam Medical Center) PRESENTER	Dr. Shelly has nothing to disclose.
Jack (Yaakov) Pepys	Mr. Pepys has nothing to disclose.
Ronen Stoff	No disclosure on file
Roni Ramon-Gonen	No disclosure on file
Guy Ben Betzalel	No disclosure on file
Amir Dori, MD, PhD (Sheba Medical Center)	Dr. Dori has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TEVA. Dr. Dori has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda . Dr. Dori has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Dori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medison Pharma. Dr. Dori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medison Pharma. The institution of Dr. Dori has received research support from Biogen. The institution of Dr. Dori has received research support from Pfizer. The institution of Dr. Dori has received research support from Alnylam therapeutics. Dr. Dori has received intellectual property interests from a discovery or technology relating to health care.