Progressive multifocal leukoencephalopathy is a rare condition caused by the polyomavirus JC (JCV) affecting almost exclusively immunosuppressed individuals. Treatment strategies are limited and generally focus on immune reconstitution. Inhibition of Programmed cell death protein 1 (PD-1) has been associated with reduced CSF JC viral load and clinical stabilisation or improvement in 5 of 8 patients reported in a previous case series (Cortese et al., 2019)[i]. Here, we report three cases of PML in patients without HIV or immunosuppressive treatment who were treated with the checkpoint inhibitor pembrolizumab in an attempt to increase CD4+ and CD8+ T-cell activity against JCV. At time of submission, disease progression had halted in 2 of 3 patients (median follow-up=10months, 1-22months). We will detail presentation and disease course and discuss challenges experienced in the management of these patients.

[i] Cortese I, Muranski P, Enose-Akahata Y, Ha SK, Smith B, Monaco M, Ryschkewitsch C, Major EO, Ohayon J, Schindler MK, Beck E, Reoma LB, Jacobson S, Reich DS, Nath A. Pembrolizumab Treatment for Pro- gressive Multifocal Leukoencephalopathy. N Engl J Med. 2019 Apr 25;380(17):1597-1605. doi: 10.1056/NEJMoa1815039. Epub 2019 Apr 10. PMID: 30969503.