Progressive Multifocal Leukoencephalopathy in a Patient on Ocrelizumab Monotherapy
James Sul1, Arpan Patel1, Marc L. Gordon1, Jared Steinklein2, Shayna Sanguinetti1, Bidyut Pramanik2, Zachary Orban3, Igor Koralnik3, Asaff Harel1
1Northwell Health-Dept. of Neurology, 2Northwell Health, 3Rush University Medical Center
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.

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.

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