1766. Osimertinib-Associated Progressive Multifocal Leucoencephalopathy

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of white matter in the central nervous system (CNS) caused by reactivation of John Cunningham (JC) virus. Drug-induced PML is increasingly reported with the widely used biological immunosuppressant drugs and molecular targeted antineoplastic agents. Monoclonal antibodies were the pioneer drugs to be associated with PML including the prototypical natalizumab. METHODS: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been rarely described in this context with few case reports of ibrutinib-associated PML. Osimertinib, a third-generation EGFR TKI, was recently FDA-approved for the first-line treatment of metastatic non-small-cell lung cancer (NSCLC), and to the best of our knowledge has never been associated with PML. We describe a case report of a rapidly progressive PML likely associated with osimertinib therapy. RESULTS: A 85-year-old female with history of NSCLC, on osimertinib, was admitted with progressively worsening left hemiparesis, facial palsy, unsteady gait, recurrent falls, and episodic confusion over a period of month. Brain magnetic resonance imaging revealed foci of non-enhancing increased T2 and fluid-attenuated inversion recovery (FLAIR) signal intensity in the periventricular and bilateral cerebral subcortical white matter. MRI cervical spine was unremarkable for acute enhancing lesions. Cerebrospinal fluid (CSF) was unremarkable for infectious etiology, oligoclonal bands, and cytology. The patient was readmitted 2 weeks later with worsening neurological deficits and new lesions in the bilateral middle cerebellar peduncles, pons, midbrain, and cerebral white matter. Positive CSF JC virus PCR lead to the final diagnosis of “probable” PML. Biopsy was deferred for high clinical suspicion of PML and procedural risks outweighing benefits. Osimertinib was likely contributing to PML in the absence of other immunosuppression. CONCLUSION: Inhibition of tyrosine kinase-dependent pathways can potentially aid in the replication of JC virus per previously reported ibrutinib-associated PML. Clinicians should be aware of PML risk in patients on osimertinib and TKI therapy, especially those with positive serum JC virus serology. [Image: see text] [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.