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Ofatumumab Treatment and Rare Viral Infection of the Brain : A Case Study in CLL

By: Melissa Steele-Ogus
Posted: Wednesday, May 20, 2020

Progressive multifocal leukoencephalopathy is a rare but serious demyelinating disease caused by the John Cunningham virus (JCV). This virus is found in up to 90% of the population and is usually nonpathogenic, but it can cause disease in immunosuppressed or immunodeficient individuals. B-cell–depleting immunotherapies, including rituximab and natalizumab, have been found to cause such vulnerability to JCV. Although progressive multifocal leukoencephalopathy has not been described in patients treated by ofatumumab, a case study of a patient with chronic lymphocytic leukemia (CLL) who presented with this viral infection after ofatumumab treatment was published in the Journal of Medical Case Reports by James Forryan, MbCHBand Jun Yong, MbCHB, of The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool.

A 68-year-old man arrived at the emergency department with diminished mobility and confusion; upon examination, he received a 14 of 15 on the Glasgow Coma Scale. The patient had completed treatment for TP53-negative CLL 2 months prior and had received 6 cycles of ofatumumab and chlorambucil. Routine bloodwork was normal, but an MRI showed frontal lobe white matter hyperintensities. Additionally, cerebrospinal fluid analysis revealed a JCV infection, and the patient was diagnosed with progressive multifocal leukoencephalopathy. The patient was discharged to hospice care and died 3 months later.

Although the relationship between B-cell depletion and JCV pathogenesis is unexplored, the authors suggest that B cells may play a role in “modifying the T-cell–mediated control of JCV infection.” Thus, the authors advised: “[Progressive multifocal leukoencephalopathy] should take its place in any differential list for a patient receiving B-cell–depleting [monoclonal antibodies] who presents with new neurology and cognitive defects, as in our case.”

Disclosure: The authors reported no conflicts of interest.

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