Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Apr 25;380(17):1597-1605.
doi: 10.1056/NEJMoa1815039. Epub 2019 Apr 10.

Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy

Irene Cortese  1 , Pawel Muranski  1 , Yoshimi Enose-Akahata  1 , Seung-Kwon Ha  1 , Bryan Smith  1 , MariaChiara Monaco  1 , Caroline Ryschkewitsch  1 , Eugene O Major  1 , Joan Ohayon  1 , Matthew K Schindler  1 , Erin Beck  1 , Lauren B Reoma  1 , Steve Jacobson  1 , Daniel S Reich  1 , Avindra Nath  1
Affiliations
Clinical Trial

Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy

Irene Cortese et al. N Engl J Med. .

Abstract

Background: Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored. Programmed cell death protein 1 (PD-1) is a negative regulator of the immune response that may contribute to impaired viral clearance. Whether PD-1 blockade with pembrolizumab could reinvigorate anti-JC virus immune activity in patients with PML was unknown.

Methods: We administered pembrolizumab at a dose of 2 mg per kilogram of body weight every 4 to 6 weeks to eight adults with PML, each with a different underlying predisposing condition. Each patient received at least one dose but no more than three doses.

Results: Pembrolizumab induced down-regulation of PD-1 expression on lymphocytes in peripheral blood and in cerebrospinal fluid (CSF) in all eight patients. Five patients had clinical improvement or stabilization of PML accompanied by a reduction in the JC viral load in the CSF and an increase in in vitro CD4+ and CD8+ anti-JC virus activity. In the other three patients, no meaningful change was observed in the viral load or in the magnitude of antiviral cellular immune response, and there was no clinical improvement.

Conclusions: Our findings are consistent with the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus; clinical improvement or stabilization occurred in five of the eight patients who received pembrolizumab. Further study of immune checkpoint inhibitors in the treatment of PML is warranted. (Funded by the National Institutes of Health.).

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources