Myasthenia gravis and Guillain-Barré syndrome adverse events with immune checkpoint inhibitors.

Abstract

37 Background: Immune checkpoint inhibitors (ICI) have provided landmark breakthrough achieving success in prolonging survival in multiple cancer types. As a new class of therapy immune related serious adverse drug reactions (sADRs) have had limited reporting. This includes neurologic based, with reports limited to clinical trials and case-based. Ours is the largest database analysis to date reporting neurological adverse events after ICI therapy. Methods: We analyzed the FDA Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, and ipilimumab two years prior their FDA approval to September 2017, to include all cases reported with Guillain-Barré syndrome (GBS), Myasthenia gravis, ocular myasthenia, and myasthenic syndrome after the usage of ICI. Results: A total 35,726 cases were reported in FAERS. We identified a total of 263 cases of which 121 (46%) were GBS, 112 (42.6%) myasthenia gravis, 22 myasthenic syndrome (8.4%), and 8 (3%) ocular myasthenia. The mean age in our study was 66 years, with 63% being male. The majority of the cases were reported in the United States (49%), followed by Japan (10%), France (6%), and Australia (5.7%). Over 30% of patients presented more than one significant symptom. Around 20% of these patients were taking more than one immune checkpoint inhibitor, combining ipilimumab with either nivolumab or pembrolizumab. A significantly higher proportion of patients with GBS taking more than one ICI (28.1%, p = 0.013). Nivolumab was the most common ICI in patients with myasthenia gravis, myasthenic syndrome, and ocular myasthenia, while ipilimumab was the most common in patients with GBS. Sixty four percent of these patients required hospitalization, 17% were reported as life threatening events, 7% resulted in disability, and 22% died. Conclusions: Neurological adverse events associated with ICI are relatively uncommon, but can have serious clinical consequences. Recognizing and detailing neurological immune syndromes in relation to ICI therapy are essential in the oncological and neurological practice due to the growing usage of these agents in cancer treatment.