Sequential treatment of progressive multifocal leukoencephalopathy with intravenous immunoglobulins and pembrolizumab

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the CNS caused by the human polyomavirus 2 (JCV). PML predominantly occurs in immunocompromised patients. To date, no specific antiviral treatment exists, leaving only restoration of the immune system as possible treatment. In 2019, the monoclonal antibody pembrolizumab was reported as a potential treatment option in PML in a case series. Following case reports could not thoroughly confirm a positive outcome. Pembrolizumab targets the inhibitory programmed cell death protein 1 (PD-1) receptor on lymphocytes and is associated with beneficial expansion of pre-existing virus-specific T cells. Here we describe a patient with PML who benefited from combined treatment with intravenous immunoglobulins, maraviroc, and pembrolizumab.

Keywords: Follicular lymphoma; Intravenous immunoglobulins; Pembrolizumab; Progressive multifocal leukoencephalopathy; Rituximab.

Fig. 1

MRI of the head during treatment with pembrolizumab. Shown is a panel with sequential MRI scans of the head from July 2019 (A), before the third pembrolizumab infusion in January 2020 (B), the fifth pembrolizumab infusion in February 2020 (C), and after the final treatment with pembrolizumab in a follow-up examination in August 2020 (D). Shown sequences are T1 (A–D), T2-weighed (B–C) or FLAIR (A, D), DWI (A–D), and T1 postcontrast (B–C)

Fig. 2

Frequencies of JC virus–specific CD4⁺ and CD8⁺ T cells. PBMC obtained before pembrolizumab treatment was stimulated with JC virus peptides covering the sequence of the capsid protein VP1, the small T antigen (ST), or the large T antigen (LT) for 5 h and analyzed for TNF production by flow cytometry. Stimulation with Staphylococcus aureus toxin B (SEB) served as positive control and incubation of cells without addition of stimulus served as background control

Fig. 3

MRI of the head from January 2020 showing contrast enhancement. Shown is a T1 postcontrast MRI scan from January 2020. Slight gadolinium enhancement is marked with an asterisk (*)