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Brief Report
March 16, 2021

Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy

Author Affiliations
  • 1Department of Neurology, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York
  • 2Department of Neurology, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Feinstein Institutes for Medical Research, Manhasset, New York
  • 3Department of Psychiatry, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Feinstein Institutes for Medical Research, Manhasset, New York
  • 4Division of Neuroradiology, Department of Radiology, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, New York
  • 5Department of Pathology, Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, New York
  • 6Department of Psychiatry, Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, New York
  • 7MIRECC, JJ Peters VA Medical Center, Bronx, New York
  • 8Department of Neuroscience, Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, New York
  • 9Department of Pathology & Laboratory Medicine, LIJ Medical Center, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York
  • 10Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
  • 11Division of Neuro-Immunology, Department of Neurology, Lenox Hill Hospital, North Shore University Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
JAMA Neurol. 2021;78(6):736-740. doi:10.1001/jamaneurol.2021.0627
Key Points

Question  Can ocrelizumab contribute to the development of progressive multifocal leukoencephalopathy?

Findings  In this case report, progressive multifocal leukoencephalopathy was observed in a 78-year-old patient with progressive multiple sclerosis who had been treated with ocrelizumab for 2 years without prior immunotherapy. The progressive multifocal leukoencephalopathy occurrence was a result of the immunomodulatory function of ocrelizumab as well as age-related immunosenescence.

Meaning  This case report emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly patients.

Abstract

Importance  Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus that has no proven effective treatment. Although rare cases of PML have occurred with other anti-CD20 therapies, there had been no prior cases associated with ocrelizumab.

Objective  To report the first ever case of PML occurring with ocrelizumab monotherapy in a patient with progressive multiple sclerosis without prior immunomodulation.

Design, Setting, and Participant  This case was reported from an academic medical center. The patient had multiple sclerosis while receiving ocrelizumab monotherapy.

Exposures  Ocrelizumab monotherapy.

Results  A 78-year-old man with progressive multiple sclerosis treated with ocrelizumab monotherapy for 2 years presented with 2 weeks of progressive visual disturbance and confusion. Examination demonstrated a right homonymous hemianopia, and magnetic resonance imaging revealed an enlarging nonenhancing left parietal lesion without mass effect. Cerebrospinal fluid revealed 1000 copies/mL of JC virus, confirming the diagnosis of PML. Blood work on diagnosis revealed grade 2 lymphopenia, with absolute lymphocyte count of 710/μL, CD4 of 294/μL (reference range, 325-1251/μL), CD8 of 85/μL (reference range, 90-775/μL), CD19 of 1/μL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia that preceded ocrelizumab (absolute lymphocyte count range, 800-1200/μL). The patient’s symptoms progressed over weeks to involve bilateral visual loss, right-sided facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated. The patient nevertheless declined rapidly and ultimately died. PML was confirmed at autopsy.

Conclusions and Relevance  In this case report, PML occurrence was likely a result of the immunomodulatory function of ocrelizumab as well as age-related immunosenescence. This case report emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly patients.

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