Pembrolizumab for treatment of progressive multifocal leukoencephalopathy in primary immunodeficiency and/or hematologic malignancy: a case series of five patients

J Neurol. 2022 Feb;269(2):973-981. doi: 10.1007/s00415-021-10682-8. Epub 2021 Jul 1.


Progressive multifocal leukoencephalopathy is a rare opportunistic infection of the brain by John Cunningham polyomavirus in immune-compromised patients. In cases where no overt option for immune reconstitution is available [e.g., in patients with primary immunodeficiency (PID)], the disease is lethal in the majority of patients. Immune checkpoint inhibition has been applied in recent years with mixed outcomes. We present four novel patients and the follow-up of a previously published patient suffering from progressive multifocal leukoencephalopathy (PML) due to PID and/or hematologic malignancy who were treated with the immune checkpoint inhibitor pembrolizumab. In two patients with PID, symptoms improved and stabilized. One patient died because of worsening PML another of intracranial hemorrhage which was unrelated to PML or its treatment with pembrolizumab. The fifth patient suffered from PID and died of a pre-existing immune dysregulation, possibly exacerbated by pembrolizumab. The long-term follow-up of the first patient provides support for therapeutic decisions during this therapy and is the longest published clinical course of a patient with checkpoint inhibition for PML. We conclude that pembrolizumab can control PML symptoms long term in a subgroup of patients with PID, in our cases for 21 and 36 months. However, therapy must be started early because symptoms are only partially reversible. In light of severe adverse events, application of pembrolizumab is only justified if the prognosis for the individual patient is very poor.

Keywords: Autoimmunity; Hematologic malignancy; PID; PML; Pembrolizumab.

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Hematologic Neoplasms*
  • Humans
  • JC Virus*
  • Leukoencephalopathy, Progressive Multifocal* / drug therapy


  • Antibodies, Monoclonal, Humanized
  • pembrolizumab