Brighton and Sussex University Hospitals NHS Trust
Hurstwood Park Neurological Centre

Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Poster Presentation

P0362 - Novel treatment approach for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing remitting multiple sclerosis (ID 967)

Speakers
Presentation Number
P0362
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Progressive multifocal leukencephalopathy (PML) due to the polyoma JC virus (JCV), remains an untreatable viral infection. Aside from addressing the underlying cause of immunodeficiency, there remains no evidenced-based treatment for PML. PML is rarely seen in fingolimod-treated relapsing remitting multiple sclerosis (RRMS) patients.

Objectives

We present a 62 year-old man with RRMS of 20-years duration treated with fingolimod for 6 years who developed PML and discuss the response to a PD-1 inhibitor, pembrolizumab.

Methods

Onset of illness was insidious with progressive left leg weakness, gait unsteadiness, slurred speech, double vision, asymmetric cerebellar ataxia, bilateral internuclear ophthalmoplegia and spastic paraparesis. Expanded disability status scale (EDSS) increased from 6.0 to 6.5. Fingolimod was immediately withheld.

Results

Magnetic resonance imaging (MRI) scan demonstrated new, patchy, non-enhancing hyperintense lesions within the white matter of frontal lobes, right thalamus and brainstem. 160 copies/ml of JCV-DNA were detected in the cerebrospinal fluid (CSF). Mirtazepine dose was increased to 45mg daily. Despite a few weeks’ clinical stability, MRI appearances and JCV-DNA copies worsened over the next 3 weeks followed by gait deterioration. Maraviroc 300mg twice daily was then introduced. Subtle punctate contrast enhancement, suggestive of a mild immune reconstitution inflammatory syndrome (IRIS), was transiently seen within the midbrain and right frontal areas of signal change 6 weeks after fingolimod cessation, followed by a single focal-to-generalised tonic clonic seizure. EDSS increased to 8.0. Mefloquine 250mg weekly and 3 monthly doses of 200mg pembrolizumab, were administered. Serial CSF examinations and several imaging modalities including spectroscopy and fused FDG-PET-MRI were used to distinguish between PML, PML-IRIS and MS activity. The patient’s symptoms and “PML lesions” on brain MRI scans remained stable, although a handful of small, enhancing ovoid lesions developed between the first two doses of pembrolizumab. Following the second dose of pembrolizumab, a sustained but gradual improvement in imaging and examination parameters was observed with JCV-DNA becoming undetectable 16 weeks following fingolimod withdrawal. EDSS improved from 8.0 to 6.5.

Conclusions

This case highlights several challenges of managing PML, a highly life threatening condition. To our knowledge this is the first case of combined therapy and use of pembrolizumab in a fingolimod-associated PML.

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