Atezolizumab-Induced Aseptic Meningitis in Patients with NSCLC

Abstract

IntroductionDuring treatment with immune checkpoint inhibitors, immune-related adverse events sometimes occur, and their management is a critical concern associated with such treatment. Encephalitis and meningitis are some of the critical immune-related adverse events. Atezolizumab is an immune checkpoint inhibitor that inhibits the programmed cell death-ligand. Encephalitis and meningitis were reported in 0.8% of the patients in the atezolizumab versus docetaxel in patients with previously treated NSCLC. However, none of the reports have clarified the details concerning atezolizumab-induced encephalitis and meningitis, including their background, time of onset, treatment, and therapeutic course. We herein report about three patients who experienced atezolizumab-induced meningitis in our department. MethodsOf the 29 patients who received atezolizumab in our department between October 2015 and September 2018, three developed aseptic meningitis. We retrospectively examined their clinical, radiologic, and cytologic features. ResultsIn all three cases, a depressed level of consciousness followed fever in cycle 1, days 15 and 16 after administration of atezolizumab. Cerebrospinal fluid examination revealed that the number of cells was not increased despite the protein level being high. No definite malignant cells were identified in the cerebrospinal fluid in any of the three cases. Only one patient exhibited abnormal enhancement along the lines of the corpus callosum on magnetic resonance imaging. On the basis of these findings, the patients were diagnosed with atezolizumab-induced meningitis. After the administration of methylprednisolone (1000 mg for 3 d), they promptly became conscious and alert. ConclusionAtezolizumab-induced meningitis may have some specific features, such as a characteristic development period, findings in magnetic resonance imaging, and premonitory symptoms.