Abstract Details

Title Progressive Multifocal Leukoencephalopathy in a Patient on Ocrelizumab Monotherapy

Topic Multiple Sclerosis

Presentation(s) S29 - Multiple Sclerosis: Disease-modifying Therapy (1:00 PM-1:12 PM)

Poster/Presentation
Number 001

Objective To report a case of progressive multifocal leukoencephalopathy (PML) occurring after two years of ocrelizumab monotherapy in a patient with progressive multiple sclerosis (MS) without prior immunomodulatory medication.

Background

PML is an untreatable, life-threatening, opportunistic infection caused by the JC virus (JCV), occurring in individuals with impaired cell-mediated immunity. While anti-CD20 therapies primarily target B-cells, they also mildly decrease CD4 and CD8 levels. Though rare cases of PML have occurred with rituximab, there had been no prior PML cases associated with ocrelizumab. Previous PML cases after ocrelizumab initiation were “carry-over” cases related to prior natalizumab or fingolimod use, and ocrelizumab was deemed non-contributory.

Design/Methods Case report: A 78-year-old man with progressive MS treated with ocrelizumab monotherapy for two years without prior immunomodulatory medications presented with two weeks of progressive visual disturbance and confusion. Exam demonstrated a right homonymous hemianopia and MRI revealed an enlarging non-enhancing left parietal lesion without mass effect. CSF PCR revealed 1,000 copies/ml of JCV, confirming the diagnosis of PML. Blood work upon diagnosis revealed grade-2 lymphopenia, with absolute lymphocyte count (ALC) 710/uL, CD4 294/uL (reference 325-1251), CD8 85/uL (reference 90-775), CD19 1/uL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective analysis revealed intermittent grade-1 lymphopenia that preceded ocrelizumab therapy (ALC range 800-1200/uL). The patient’s symptoms progressed over weeks to involve bilateral visual loss, right facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated.

Results This is the first occurrence of PML directly associated with ocrelizumab monotherapy. Subsequent course will be presented.

Conclusions PML occurrence may have been multifactorial, due to a combination of the immunomodulatory function of ocrelizumab, possible immune senescence, and preceding mild lymphopenia. This case emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections, such as the elderly.

Authors/Disclosures
James Sul, MD (Northwell Health-Dept. of Neurology) PRESENTER	No disclosure on file
Arpan Patel, MBBS (University of Kansas Medical Center)	Dr. Patel has nothing to disclose.
Marc L. Gordon, MD, FAAN (Northwell Health)	Dr. Gordon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Labcorp. Dr. Gordon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Corium. Dr. Gordon has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Morgan and Morgan. Dr. Gordon has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Wilson, Elser, Moskowitz, Edelman & Dicker. The institution of Dr. Gordon has received research support from National Institute on Aging. The institution of Dr. Gordon has received research support from Novo Nordisk. The institution of Dr. Gordon has received research support from Alector. The institution of Dr. Gordon has received research support from Janssen. The institution of Dr. Gordon has received research support from AbbVie.
	No disclosure on file
Shayna Sanguinetti, MD (Northwell Health)	Dr. Sanguinetti has nothing to disclose.
	No disclosure on file
Zachary Orban (Northwestern University)	No disclosure on file
Igor J. Koralnik, MD, FAAN (Northwestern University)	Dr. Koralnik has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Investigation. The institution of Dr. Koralnik has received research support from National Institutes of Health. Dr. Koralnik has received publishing royalties from a publication relating to health care.
Asaff Harel, MD	Dr. Harel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Harel has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Harel has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Expert Institute.

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