PML with Fingolimod_Final[54].pdf (639.33 kB)
Management approach including pembrolizumab for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing-remitting multiple sclerosis
journal contribution
posted on 2023-06-10, 05:38 authored by Andrew W Barritt, Esther Das, Nadine Morley, Matthew Seymour, Romi Saha, Jaime Vera RojasJaime Vera Rojas, Sriram Vundavalli, Sabina Dizdarevic, Richard Nicholas, Joseph R Berger, Leonora K FisnikuA 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.
History
Publication status
- Published
File Version
- Accepted version
Journal
Multiple Sclerosis JournalISSN
1352-4585Publisher
SAGE PublicationsExternal DOI
Page range
e13524585221137279 1-6Event location
EnglandDepartment affiliated with
- Global Health and Infection Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-12-09First Open Access (FOA) Date
2022-12-09First Compliant Deposit (FCD) Date
2022-12-09Usage metrics
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