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Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab
Arpan Patel1, James Sul1, Marc L Gordon2,3
1Department of Neurology, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York.
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.
Insights
This case report details the first instance of progressive multifocal leukoencephalopathy (PML) in a patient on ocrelizumab monotherapy. The rare JC virus infection highlights risks associated with this multiple sclerosis treatment.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Oncology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare, fatal opportunistic infection caused by the JC virus, typically seen in immunocompromised individuals.
- While other anti-CD20 therapies have been linked to rare PML cases, none had been reported with ocrelizumab monotherapy.
- Ocrelizumab is a B-cell depleting therapy used for multiple sclerosis.
Observation:
- A 78-year-old male with progressive multiple sclerosis developed PML while on ocrelizumab monotherapy for two years.
- Symptoms included visual disturbances and confusion, with MRI revealing a parietal lesion and CSF confirming JC virus.
- The patient experienced lymphopenia and rapid neurological decline despite treatment cessation and initiation of pembrolizumab.
Findings:
- The first documented case of PML associated with ocrelizumab monotherapy in a patient with no prior immunomodulatory treatment.
- JC virus was detected in cerebrospinal fluid, confirming PML.
- Autopsy confirmed PML, with findings likely linked to ocrelizumab's immunomodulatory effects and age-related immune decline.
Implications:
- This case underscores the potential risk of PML with ocrelizumab, even in the absence of prior immunosuppression.
- Physicians must carefully weigh the risks and benefits of ocrelizumab, particularly in elderly patients or those with other risk factors for infection.
- Enhanced vigilance and patient monitoring are crucial for early detection of opportunistic infections during ocrelizumab therapy.
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