Background: The use of monoclonal antibodies in various settings has been linked to the development of progressive multifocal leukoencephalopathy (PML). Whilst this association is well-described with agents such as rituximab and natalizumab, the literature describing the occurrence of PML with ofatumumab therapy (especially in a haematology setting) is sparse. This case aims to draw attention to the above association with a particular focus on the mechanisms by which B-cell-depleting therapy can precipitate PML during the treatment of haematological malignancy.
Case presentation: A 68-year-old Caucasian man presented with acute-on-subacute confusion and reduced mobility. He had a history of chronic lymphocytic leukaemia for which he had completed six cycles of ofatumumab and chlorambucil 2 months prior to presentation. Biochemistry, physical examination and imaging were unremarkable on admission. Subsequent neurological examination demonstrated diminished reflexes and an extensor right plantar, while magnetic resonance imaging (MRI) assessment revealed white matter hyperintensities in the frontal lobes with restricted diffusion surrounding these areas. Cerebrospinal fluid (CSF) analysis demonstrated normal cell counts and chemistry but detected John Cunningham virus (JCV) via polymerase chain reaction (PCR), with a quantitative value of 41,850 gEg/ml. CSF immunophenotyping excluded malignant processes. A diagnosis of PML was confirmed, and with the support of palliative care, the patient was discharged to a hospice for ongoing care with the family's agreement.
Conclusion: PML remains a rare complication of ofatumumab treatment. Nevertheless, clinicians should maintain a certain level of suspicion for this risk, especially in the context of patients presenting with clinical syndromes of encephalopathy and focal neurologic deficits. Furthermore, research to better our understanding of the manifold links between B-cell function and JCV regulation could provide valuable information for use in the future prevention and treatment of PML.
Keywords: Progressive multifocal leukoencephalopathy, Chronic lymphocytic leukaemia, Ofatumumab, Monoclonal antibodies, B-cell-depleting therapy.