Promising Results Published for Pembrolizumab to Treat Progressive Multifocal Leukoencephalopathy

As published in the New England Journal of Medicine, positive results have been seen in a small study of pembrolizumab (Keytruda; Merck, Kenilworth, NJ) for treatment of progressive multifocal leukoencephalopathy (PML), caused by the JC virus. Of the 8 individuals with PML who were treated with pembrolizumab in this open-label study, 5 had clinical improvement or stabilization of PML. 

For those who had clinical improvement, there was also a reduction in the cerebrospinal fluid (CSF) JC viral load and an increase in in vitro CD4+ and CD8+—JC virus activity. Although all 8 individuals experienced downregulation of programmed cell death protein-1 (PD-1) expression in blood and CSF samples, for the 3 people without clinical improvement, there was no meaningful change in viral load or cellular antiviral immune response. 

Pembrolizumab is FDA-approved for treatment of multiple cancer types. Therapeutic effects are thought to be through blocking the interaction between PD-1 and programmed cell death protein L1 (PD-L1) and PD-L1. This interaction normally limits inflammation and neoplasms that express PD-L1 block that and thereby increase inflammation and limit the immune response to the neoplasm. 

“We found both PD-1 and PD-L1 proteins in the infected parts of brains of patients with PML,” said Irene Cortese, M.D., director of the NINDS Neuroimmunology Clinic and first author of the paper. “This led us to ask whether pembrolizumab could be a potential treatment for PML.”

The JCV is common and present in 30-60% of people; it is usually innocuous, but people who have their immune system suppressed by treatments for autoimmune disease such as multiple scleroris (MS) may have increased risk of PML. 

 “Previous attempts to treat PML have been disappointing,” said Dr. Cortese, “so we are very encouraged by these preliminary results.”