TY - JOUR
T1 - Progressive Multifocal Leukoencephalopathy in a Patient with Progressive Multiple Sclerosis Treated with Ocrelizumab Monotherapy
AU - Patel, Arpan
AU - Sul, James
AU - Gordon, Marc L.
AU - Steinklein, Jared
AU - Sanguinetti, Shayna
AU - Pramanik, Bidyut
AU - Purohit, Dushyant
AU - Haroutunian, Vahram
AU - Williamson, Alex
AU - Koralnik, Igor
AU - Harel, Asaff
N1 - Funding Information:
grants (no direct compensation) from AbbVie, Eisai, Janssen, and MSD (Merck) and personal fees from Eisai (advisory board) and METiS Pharmaceuticals (consultant) outside the submitted work. Dr Haroutunian reports grants from the National Institutes of Health outside the submitted work. Dr Williamson reports personal fees from Springer Nature Switzerland AG royalties outside the submitted work. Dr Koralnik reports personal fees from UpToDate chapter about progressive multifocal leukoencephalopathy outside the submitted work. Dr Harel reports personal fees from Teva Pharmaceuticals, Alexion Pharmaceuticals, Biogen, and Banner Life Sciences and grants from National Multiple Sclerosis Society and Consortium of Multiple Sclerosis Centers outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - 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..
AB - 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..
UR - http://www.scopus.com/inward/record.url?scp=85102532743&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102532743&partnerID=8YFLogxK
U2 - 10.1001/jamaneurol.2021.0627
DO - 10.1001/jamaneurol.2021.0627
M3 - Article
C2 - 33724354
AN - SCOPUS:85102532743
SN - 2168-6149
VL - 78
SP - 736
EP - 740
JO - JAMA Neurology
JF - JAMA Neurology
IS - 6
ER -
