Autoimmune Encephalitis Related to Cancer Treatment with Immune Checkpoint Inhibitors: Systematic Review

Abstract

BACKGROUND. Immune checkpoint inhibitors (ICPI) are a game changer in the treatment of various metastasized cancers, but emerging reports of adverse events, including ICPI-associated autoimmune encephalitis (ICPI-AIE), are concerning. We aimed to collect all published cases of ICPI-AIE to identify the salient clinical and laboratory features of this disorder. METHODS. We searched PubMed, The Cochrane Library and Embase for ICPI-AIE cases from the first description in 2015 until 01/2020 using standard bibliographic measures including PRISMA guidelines and pre-registration with PROSPERO (CRD42019139838). RESULTS. Thirty-nine studies met inclusion criteria, resulting in 54 ICPI-AIE patients (mean age 58.6 years; 43% females). Common cancers included melanoma (30%) and non-small cell lung cancer (30%). Brain metastases were found in 16 patients (30%). The most frequent ICPI was nivolumab (61%). Onset of ICPI-AIE occurred on average after 3.5 treatment cycles, but very early and late presentations were common. Non-limbic AIE was roughly twice as frequent as limbic AIE (p<0.05). The most common laboratory abnormalities included bitemporal FLAIR lesions on MRI, continuous slow waves and diffuse slowing on EEG, and monocytic pleocytosis on cerebrospinal fluid analysis. Of note, intraneuronal antibodies were more frequent than neuronal surface antibodies, and logistic regression identified the presence of intracellular antibodies as a significant predictor for lack of improvement after 1st line immunotherapy (p<0.05). CONCLUSIONS. ICPI-AIE consists of a heterogenous group of conditions. Neurologists will likely encounter ICPI-AIE more often in the future, but important unresolved questions include the exact pathophysiological mechanisms, the epidemiology and the best treatment approaches associated with ICPI-AIE.

Neurological adverse events of immune checkpoint blockade: from pathophysiology to treatment

“…The patients with onconeural autoantibodies displayed more commonly brain MRI abnormalities, whereas seronegative encephalitis was more often characterized by inflammatory CSF and fever, thus more strictly fulfilling a diagnosis of ir-meningitis, known to have a good prognosis and responsiveness to steroids [7,29 ▪▪ ]. Accordingly, patients with onco-neuronal antibodies showed a poorer prognosis compared with seronegative patients and were refractory to steroids, as well as to humoral-targeted treatments (IVIG or plasmapheresis or rituximab) [27,31] likely because of the T-cell mediated mechanisms behind these syndromes.…”

Neurological Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Perspectives and New Development

“…41 A systematic review also reported that early and late ICI-related encephalitis were possible. 42 In addition, not all irAEs will disappear when antitumor treatment is stopped; some late-irAEs could occur a year after first application. Interestingly, a multicenter study identified that neurological late-irAEs are the only type of irAEs which tends to occur late (>12 months) rather than early (⩽12 months) in melanoma and NSCLC patients.…”

Encephalitis Induced by Durvalumab During Treatment of Metastatic Small-Cell Lung Cancer: Illustrative Case and Review of the Literature

“…Patient Hospitalization in Neurology ward with ICU facility is suggested (Table 4). 19 The treatment approach depends on the severity of the toxicity. The Common Terminology Criteria for Adverse Events (CTCAE), are commonly used for grading treatments toxicity, using a 5-point scale of grading, when grade I is related to mild symptoms and grade V related to death (Table 5).…”