Treatment of progressive multifocal leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive demyelinating disease of the central nervous system caused by John Cunningham polyomavirus (JCV), a globally seroprevelant virus that commonly causes a silent or benign infection. However, in immunocompromised patients JCV can be reactivated. In this situation, most organs remain unaffected, but multiplication within oligodendrocytes causes lytic brain lesions resulting in progressive motor dysfunction, cognitive impairment, and visual deficits. Although some strategies are available for treatment, particularly if recognised early, PML has an overall mortality of 30–50% and can result in substantial morbidity. Progressive multifocal leukoencephalopathy is thankfully rare and most commonly associated with lymphoproliferative disease or advanced human immunodeficiency virus (HIV) infection. However, PML is now well known to be associated with the use of disease modifying therapies (DMTs) in multiple sclerosis (MS) such as natalizumab that alter cell-mediated immunity. Given the serious implications of a diagnosis of PML, patients now undergo a process of risk stratification at commencement of treatment and then selective serological testing over the course of treatment, interval magnetic resonance imaging (MRI) and regular clinical surveillance to identify any early pathological changes. Once a diagnosis is established, current treatment strategies include withdrawal of immunosuppressive therapies, plasma exchange (PLEX), mirtazapine, mefloquine as well as strategies to up regulate patient immunity. This month’s journal club reviews three new potential treatment options in the management of PML. The first paper reviews the use of pembrolizumab, the second allogeneic BK virus-specific T cells and the third filgrastim. Pembrolizumab treatment for progressive multifocal leukoencephalopathy