Sequential interleukin 2 and pembrolizumab use in progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) secondary to John Cunningham (JC) virus infection remains as yet an untreatable viral infection. Plasmapheresis, adoptive T-cell therapyies, and immune reconstitution strategies have all been used with variable success. Cortese et al.1 showed that pembrolizumab, a programmed cell death protein-1 (PD-1) checkpoint inhibitor, increases CD4+ and CD8+ activities and thereby reduces JC viral load. Five of their 8 patients did well, but the remainder, despite effective PD-1 suppression, failed to establish an anti–JC virus T-cell response. Recently, Kuepper et al.2 published a case of primary immunodeficiency with PML who demonstrated a dramatic reduction in PD-1 expression with pembroluzimab, but the patient still died. The authors would like to thank Professor David Baker, Queen Mary University of London for his helpful comments.