Arpan Patel1, James Sul1, Marc L Gordon2,3, Jared Steinklein4, Shayna Sanguinetti1, Bidyut Pramanik4, Dushyant Purohit5,6, Vahram Haroutunian6,7,8, Alex Williamson9, Igor Koralnik10, Asaff Harel11. 1. Department of Neurology, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York. 2. Department of Neurology, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Feinstein Institutes for Medical Research, Manhasset, New York. 3. Department of Psychiatry, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Feinstein Institutes for Medical Research, Manhasset, New York. 4. Division of Neuroradiology, Department of Radiology, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, New York. 5. Department of Pathology, Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, New York. 6. Department of Psychiatry, Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, New York. 7. MIRECC, JJ Peters VA Medical Center, Bronx, New York. 8. Department of Neuroscience, Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, New York. 9. Department of Pathology & Laboratory Medicine, LIJ Medical Center, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York. 10. Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois. 11. Division of Neuro-Immunology, Department of Neurology, Lenox Hill Hospital, North Shore University Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.
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.
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.
Authors: Bruce Ac Cree; Krzysztof W Selmaj; Lawrence Steinman; Giancarlo Comi; Amit Bar-Or; Douglas L Arnold; Hans-Peter Hartung; Xavier Montalbán; Eva K Havrdová; James K Sheffield; Neil Minton; Chun-Yen Cheng; Diego Silva; Ludwig Kappos; Jeffrey A Cohen Journal: Mult Scler Date: 2022-06-28 Impact factor: 5.855