Management approach including pembrolizumab for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing-remitting multiple sclerosis

Mult Scler. 2023 Feb;29(2):301-306. doi: 10.1177/13524585221137279. Epub 2022 Nov 30.


A 62-year-old man with relapsing-remitting multiple sclerosis developed progressive multifocal leukencephalopathy (PML) after 6 years on fingolimod. The fingolimod was immediately discontinued and preexisting mirtazepine increased. Three weeks later, with brain magnetic resonance imaging (MRI) appearances worsening and cerebrospinal fluid (CSF) JC virus (JCV) titres increasing, maraviroc was introduced. At 6 weeks, subtle punctate contrast enhancement raised the possibility of immune reconstitution inflammatory syndrome (IRIS), followed by a single focal-to-generalised tonic clonic seizure and a further deterioration in clinical disability. Mefloquine was commenced alongside three doses of pembrolizumab administered a month apart. Serial CSF examinations and several imaging modalities including spectroscopy and fused FDG-PET-MRI (18F-fluoro-deoxy-glucose-positron emission tomography-magnetic resonance imaging) were used to help distinguish between PML, PML-IRIS and rebound MS activity and guide optimal management at each stage. A handful of small, enhancing ovoid lesions developed between the first two doses of pembrolizumab, probably representative of a mild rebound phenomenon. A sustained improvement became obvious thereafter with CSF JCV-DNA undetectable 16 weeks following fingolimod withdrawal. To our knowledge, this is the first case of combined therapy and use of pembrolizumab in a fingolimod-associated PML.

Keywords: MRI; Multiple sclerosis; fingolimod; pembrolizumab; progressive multifocal leukencephalopathy.

Publication types

  • Case Reports

MeSH terms

  • Fingolimod Hydrochloride / adverse effects
  • Humans
  • JC Virus*
  • Leukoencephalopathy, Progressive Multifocal* / chemically induced
  • Leukoencephalopathy, Progressive Multifocal* / diagnostic imaging
  • Leukoencephalopathy, Progressive Multifocal* / drug therapy
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy
  • Natalizumab / adverse effects


  • Fingolimod Hydrochloride
  • pembrolizumab
  • Natalizumab