Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy

Area of Science:

• Neuroimmunology
• Viral Infections
• Oncology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a fatal opportunistic brain infection caused by the JC virus.
• Programmed cell death protein 1 (PD-1) negatively regulates immune responses, potentially impairing viral clearance in PML.
• The efficacy of PD-1 blockade with pembrolizumab for anti-JC virus immunity in PML was previously unknown.

Purpose of the Study:

• To investigate whether PD-1 blockade with pembrolizumab can reinvigorate anti-JC virus immune activity in patients with PML.
• To evaluate the clinical and virological effects of pembrolizumab treatment in PML patients.

Main Methods:

• Eight adult patients with PML received pembrolizumab (2 mg/kg every 4-6 weeks) for 1-3 doses.
• PD-1 expression on lymphocytes in peripheral blood and CSF was monitored.
• JC viral load in CSF and in vitro anti-JC virus cellular immune activity (CD4+ and CD8+) were assessed.

Main Results:

• Pembrolizumab down-regulated PD-1 expression on lymphocytes in all eight patients.
• Five patients experienced clinical improvement or stabilization, with reduced JC viral load and increased anti-JC virus CD4+ and CD8+ T-cell activity.
• Three patients showed no significant changes in viral load, immune response, or clinical status.

Conclusions:

• Pembrolizumab may reduce JC viral load and enhance anti-JC virus cellular immunity in some PML patients.
• Clinical improvement or stabilization was observed in 5/8 patients treated with pembrolizumab.
• Further research into immune checkpoint inhibitors for PML treatment is warranted.