NTOX-03. NEUROLOGIC COMPLICATIONS OF CTLA-4 INHIBITOR IPILIMUMAB

Abstract

Neurologic complications are an increasingly recognized complication of the use of the immune checkpoint inhibitors in the treatment of solid tumors. The clinical spectrum of the CTLA-4 immune checkpoint inhibitor ipilimumab associated neurologic complications and optimum treatment approach is not established. To determine the frequency, clinical spectrum and optimum treatment approach to CTLA-4 inhibitor associated neurologic complications. This single center, retrospective cohort study was conducted from the drug’s FDA approval, March 2011 to December, 2016. All patients receiving a CTLA-4 inhibitor were identified using the Mayo Cancer Pharmacy database. Patients who developed neurological symptoms in immediate temporal proximity to Ipilimumab use were included. We excluded patients who developed symptoms after subsequent immune-modulatory or cancer related treatments (e.g. PD-1 inhibitors), or patients with symptoms referable to metastatic disease. 445 patients received ipilimumab at our institution between March 2011 and January 2016. 222 (49.8%) had been evaluated by a staff neurologist at our institution during their care. 3 patients (0.6%) were felt to have neurologic phenomenon in proximity to dosing of ipilimumab which was potentially attributable to the medication while not on another immune checkpoint inhibitors. Two patients (66%) had transient self-limited cranial neuropathies (Bell’s palsy; transient diplopia). One patient (33%) had bilateral phrenic nerve inflammatory neuropathies with diaphragmatic failure and simultaneous pan-hypopituitarism while being treated with ipilimumab. In our cohort multiple patients (n= 13, 2.9%) who had previously received ipilimumab subsequently were treated with PD-1 inhibitors and developed neurologic complications. Neurological adverse events associated with the CTLA-4 inhibitor ipilimumab in our large cohort consisted of transient self-limited cranial neuropathies and one case of inflammatory amyotrophy which responded to discontinuation of ipilimumab and initiation of steroids, with an incidence of 0.6%. Discontinuation and immune rescue may be indicated.