Progressive Multifocal Leukoencephalopathy Secondary to Possible Covert Administration of Osimertinib, a Case Report. (P13-10.004)

Abstract

<h3>Objective:</h3> to report a case of rapidly progressive multifocal leukoencephalopathy with unclear cause, possibly secondary to covert administration of Osimertinib. <h3>Background:</h3> Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that was first reported in 1958. It is caused by reactivation of the John Cunningham (JC) virus. Drug-induced PML is increasingly reported in the era of molecular anti-neoplastic targeted therapy. Osimertinib, a tyrosine kinase inhibitor (TKI) was described in one case report to be associated with rapidly progressive PML, we believe our case to be the second. <h3>Design/Methods:</h3> Case report, N/A <h3>Results:</h3> 47-year-old-male with pulmonary sarcoidosis presented with worsening confusion and jerking episodes for nine months. Examination was significant for pseudobulbar affect, left sided weakness, and hyperreflexia. MRI brain showed multiple hyperintense FLAIR lesions in the subcortical white matter without enhancement. MRI cervical, thoracic, and lumbar spine was unremarkable. CT chest abdomen and pelvis was negative for malignancy but showed findings consistent with pulmonary sarcoidosis. CSF showed normal cell count and protein. CSF viral studies, bacterial studies, fungal studies, N-methyl-D-Aspartate Receptor Ab IgG CSF, NMO IgG, CSF were negative. He was found to have low total CD4 count of 118. Blood tests for infectious (including HIV), autoimmune, and paraneoplastic causes were unremarkable. He was noted to have. Brain biopsy confirmed the diagnosis of PML. There was reported concern about covert administration of Osimertinib which was available at home. The patient’s course was complicated by sepsis and he passed away after a month of hospitalization. <h3>Conclusions:</h3> This case demonstrates a challenging presentation of PML in an originally supposed immunocompetent patient. Inhibition of tyrosine kinase-dependent pathways can potentially aid in the replication of JC virus. Holding immunosuppressive therapy remains the mainstay for management for non-HIV related PML. Early recognition of this fatal etiology and its subcategory would help guide clinical management. <b>Disclosure:</b> Dr. Centofanti has nothing to disclose. Dr. Alkhoujah has nothing to disclose. Dr. Bishja has nothing to disclose.