Neurologic Immune Related Adverse Events (Iraes) In Patients With Metastatic Solid Tumors Treated With Immune Checkpoint Inhibitors: A Single Institution Retrospective Analysis

Objective: To characterize neurologic irAEs Background: Immune checkpoint inhibitors (ICIs) have shown significant antitumor activity and are approved for the treatment of multiple cancer types. ICIs are associated with a unique set of toxicities termed irAEs. This study seeks to review the incidence and clinical manifestations of patients who developed neurotoxicity with ICIs. Design/Methods: An IRB approved retrospective study involved review of charts and institutional databases. We identified patients who developed neurotoxicity while on at least one of the following ICIs: anti-CTLA4, anti-PD1 or anti-PDL1 over a 6 year period (1/1/2010–5/15/2016). Patients with primary brain tumors were excluded. Patients with brain metastases who had neurological change or decline consistent with this were not included as neurological irAEs. Results: We identified a total of 3,804 patients treated with one or more ICI during the period of review. Neurotoxicity was observed in 77 patients (2%) affecting both central and peripheral nervous systems. 26 patients (34%) received more than one ICI. Median number of doses prior to developing toxicity was 3 (1–29). Thirteen patients had >1 neurotoxicity. The various neurologic phenotypes observed in patients included: sensory neuropathy (16), encephalopathy (14), aseptic meningitis or headache (14), myasthenia gravis-like syndrome (4), myopathy or myositis (14), autonomic neuropathy (2) brachial plexitis(2), mononeuritis multiplex(3), sensorimotor neuropathy or AIDP-like syndrome(8), paraneoplastic syndromes (4) and posterior reversible encephalopathy syndrome(2). Forty-nine patients required hospital admission, 2 required ICU, and there was one death. A diagnosis of neurotoxicity was based upon the temporal association with ICIs and appropriate workup including but not limited to neurologic consultation, lumbar puncture, electrophysiologic studies, and neuroimaging. Patients were treated with drug holiday, observation, corticosteroids, plasma exchange and/or IVIG. Conclusions: As ICIs are being used with increased frequency, oncologists and neurologists should be aware of the varied manifestations of neurotoxicity in order to ensure appropriate diagnosis, work up and treatment. Disclosure: Dr. Malani has nothing to disclose. Dr. Haggiagi has nothing to disclose. Dr. Holder has nothing to disclose. Dr. Shames has nothing to disclose. Dr. Briggs has nothing to disclose. Dr. Callahan has nothing to disclose. Dr. Santomasso has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Juno Therapeutics and Kite Pharma.