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

Abstract

Atezolizumab is an available programmed death ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for the treatment of non-small cell lung cancer.Although immune checkpoint inhibitors are antitumorigenic, they have the potential to cause immune-related adverse events (irAEs), including but not limited to dermatological, gastrointestinal, hepatic, endocrine, and other less common inflammatory events including neurologic events.The incidence of irAEs remains particularly low in the central nervous system (CNS).Here, however, we present a case of irAEs in the CNS that are directly attributable to the use of atezolizumab.A 78-year-old man was referred to our hospital with complaints of confusion and fever.He had received his first dose of atezolizumab 13 days ago for recurrent metastatic lung cancer.The patient was diagnosed with a metastatic lung tumor of the left temporal lobe in January 2014.He underwent a left temporal lobectomy and positron emission tomography, which revealed lung adenocarcinoma with the upper right hilar lymph nodes positive (stage cT1cN1M1b).The patient underwent chemotherapy and radiation therapy to treat the cancer.However, in May 2018, the tumor had still progressed, and a standard treatment of atezolizumab 1200 mg per day was started intravenously.A neurological examination revealed somnolence and nuchal rigidity, with no other abnormal findings.Administration of methylprednisolone 1000 mg per day, empiric antibiotics (ceftriaxone), and acyclovir was also started intravenously.Initial brain magnetic resonance imaging (MRI) with gadolinium on day 3 showed no abnormal findings other than the left temporal lobectomy.On day 1, cerebrospinal fluid (CSF) analysis demonstrated a normal glucose level, cell count of 6/μL, protein concentration of 106 mg/dL, myelin basic protein concentration of 115.3 pg/mL, and negative cytological findings.The CSF sample was negative for bacterial cultures, and serological analysis of potential virus contamination (for herpes simplex virus 1 and 2 polymerase chain reaction, Varicella Zoster virus antibodies, Cytomegalovirus antibodies, Epstein-Barr Virus antibodies) also yielded negative results.Serological paraneoplastic autoantibodies [AMPH, CV2, PNMA2, Ri, Yo, Hu, recoverin, SOX1, titin, zic4, Tr(DNER), GAD65] were negative.Other paraneoplastic antibodies (antibodies against the voltage-gated potassium channel complex and N-methyl-D-aspartate receptors) were also negative.