Atezolizumab-induced encephalitis in metastatic lung cancer: a case report and literature review

Arakawa, Masafumi; Yamazaki, Mineo; Toda, Yumiko; Saito, Riho; Ozawa, Akiko; Kosaihira, Seiji; Kimura, Kazumi

doi:10.1016/j.ensci.2018.12.001

Cited by 23 publications

(22 citation statements)

References 8 publications

(7 reference statements)

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“…Encephalitis associated with atezolizumab has rarely been reported as an irAE; to the best of our knowledge, only three cases have been reported [4][5][6]. Encephalitis was not reported as an irAE for atezolizumab in Phases 1 and 2 of the POPLAR trial (atezolizumab vs. docetaxel for patients with previously treated non-small cell lung cancer).…”

Section: Discussionmentioning

confidence: 75%

“…Leptomeningeal enhancement or lesions of the brain parenchyma on brain magnetic resonance imaging were observed, except that two showed no abnormal findings, as in the present case. Although the management of encephalitis associated with atezolizumab has not been well-established, responses to steroid therapy were good, and further additional treatment was not required [6]. On the other hand, in some cases of encephalitis associated with nivolumab, a PD-1 inhibitor, additional treatment with immunoglobulin, or plasmapheresis was required [9,10].…”

Section: Discussionmentioning

confidence: 99%

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Atezolizumab-associated encephalitis in metastatic lung adenocarcinoma: a case report

et al. 2020

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Background: In recent years, immune checkpoint inhibitors have been widely used as a crucial therapy in malignant tumors. Immune checkpoint inhibitors can cause various autoimmune side effects called immune-related adverse events because they generate an exaggerated inflammatory response. Encephalitis associated with atezolizumab has rarely been reported as an immune-related adverse event. A case of encephalitis caused by treatment with atezolizumab is presented. Case presentation: A 56-year-old Japanese man with lung cancer previously treated with surgery and chemotherapy was admitted with high fever, consciousness disorder, and motor aphasia. His first atezolizumab treatment was 17 days earlier. Admission brain magnetic resonance imaging with gadolinium enhancement showed no abnormalities. Cerebrospinal fluid showed cell count 20/l, protein 166 mg/dl, glucose 73 mg/dl, and interleukin 6 82.9 pg/ml (normal< 8.7 pg/ml). Atezolizumab-induced encephalitis was diagnosed. His symptoms improved the day after steroid pulse therapy was started. Following steroid pulse therapy, oral prednisolone 30 mg was started and tapered. The cerebrospinal fluid findings normalized on day 14. He was discharged on day 16 without neurological sequelae. Conclusion: In this case of encephalitis associated with atezolizumab, prompt steroid pulse therapy led to a successful response, and the outcome was good. The cerebrospinal fluid level of interleukin 6 reflected the severity of the encephalitis well. Clinicians should be aware of the possibility of encephalitis after initiation of immune checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Atezolizumab-associated encephalitis in metastatic lung adenocarcinoma: a case report

et al. 2020

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“…We searched PubMed for irEncephalitis (including meningoencephalitis, encephalomyelitis, and cerebellitis) cases and identified 60 patients (Tables 1 and S1), 22,32‐73 35 (58.3%) of which were males. The median onset age was 60 years (interquartile range, IQR: 53‐69; range: 19‐83).…”

Section: Neurological Iraesmentioning

confidence: 99%

Neurological immune‐related adverse events associated with immune checkpoint inhibitors: A review of the literature

Fan

Ren

Zhao

et al. 2020

Asia-Pac J Clncl Oncology

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Immune checkpoint inhibitors (ICIs) have made a breakthrough in cancer therapy. Patients treated with ICIs may develop immune-related adverse events (irAEs) due to the upregulated activity of the immune system. With the increasing use of ICIs, irAEs are more frequently reported and have become important challenges in many patients. Neurological irAEs, which include encephalitis, myelitis, aseptic meningitis, peripheral neuropathy, myasthenia gravis, and myositis, consist of a distinct group of neuroinflammatory disorders. These disorders are rare but frequently severe with high mortality and morbidity. Patients with neurological irAEs are generally responsive to immune-modulating therapy. Therefore, early recognition and treatment are the most important ways to improve their prognosis. Here, we provide a comprehensive review of neurological irAEs associated with ICIs and focus on these affecting central nervous systems.

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“…The initial database searches retrieved a total of 603 studies, and 2 studies were manually added when checking reference lists ( Figure S1 , supplemental files ). In total, 39 studies 10,11,20–29,12,30–39,13,40–48,14–19 with 53 individual patients met inclusion criteria; the first study was published in 2015. We included data from the patient in Figure 1 , seen at our institution.…”

Section: Resultsmentioning

confidence: 99%

“…We divided patients in the following (partly overlapping) subgroups: With brain metastases (BM+) (N=16) 11,13,17,23,28,31,33,35,45,47,38,41,42,44,46 , without brain metastases (BM-) (N=38) 10,12,24–27,29–32,34,36,14,37,39,40,42,43,45,46,48,15,16,18–22 , with limbic AIE (N=16) 14,18,46,47,19,22,26,27,34,36,39,42 and extra-limbic AIE (N=38) 10,11,23–26,28–33,12,35,37,38,40–42,44–46,48,13,15–17,20–22 . Limbic AIE were determined according to criteria for AIE by Graus et al 7 One patient had bitemporal FLAIR lesions and anti-Ma2 antibodies present in CSF, but the clinical presentation was not consistent with involvement of the limbic system, there were no CSF pleocytosis or EEG activity suggestive of temporal involvement, and this patient was therefore labelled as having extra-limbic AIE.…”

Section: Resultsmentioning

confidence: 99%

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

Nersesjan

McWilliam

Krarup

et al. 2020

Preprint

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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.

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Atezolizumab-induced encephalitis in metastatic lung cancer: a case report and literature review

Cited by 23 publications

References 8 publications

Atezolizumab-associated encephalitis in metastatic lung adenocarcinoma: a case report

Atezolizumab-associated encephalitis in metastatic lung adenocarcinoma: a case report

Neurological immune‐related adverse events associated with immune checkpoint inhibitors: A review of the literature

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

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