Severe Central Nervous System Fungal Infection Following Tirabrutinib Administration in a Patient with Refractory...

Tirabrutinib, an inhibitor of Bruton's tyrosine kinase-a hub gene for primary central nervous system lymphoma proliferation-is a novel therapeutic agent for relapsed and refractory primary central nervous system lymphoma. We report a case of severe Aspergillus encephalitis following tirabrutinib administration. A man in his 50s suddenly presented with left sided hemiparesis, and neuroimaging suggested a primary central nervous system lymphoma in the right parietal lobe. The results of the tissue biopsy revealed a diagnosis of CD20-positive diffuse large B-cell lymphoma. Despite treatment with high-dose methotrexate combined with rituximab, neurological symptoms rapidly deteriorated. We suspected that the growth of the tumor led to an impending brain herniation, so we planned radiation therapy. However, the patient contracted coronavirus disease 2019. Therefore, we decided to administer tirabrutinib, which can be administered orally. The tumor shrank dramatically, and improvement in neurological symptoms was observed. However, due to onset of liver dysfunction, tirabrutinib was discontinued. Immediately thereafter, the primary central nervous system lymphoma began to progress again, necessitating the re-administration of tirabrutinib. Concurrently, a cerebral abscess developed in the basal ganglia. Subsequently, a fatal subcortical hemorrhage occurred. Brain tissue obtained during hematoma evacuation led to a histological diagnosis of Aspergillus cerebral vasculitis. We started treatment with voriconazole first, and then added amphotericin B, but multiple cerebral abscesses developed and progressed to encephalitis, resulting in death. Burton's tyrosine kinase is a gene crucial for the general antifungal immunity, and when using Burton's tyrosine kinase inhibitors, physician should always be mindful of preventing, detecting early, and addressing fungal infections to avoid fatal adverse events like in this case.