Ofatumumab-Related Progressive Multifocal Leukoencephalopathy: Case Study in CLL
Posted: Thursday, September 30, 2021
A patient profile published in the journal Internal Medicine describes a 79-year-old man with chronic lymphocytic leukemia (CLL) diagnosed with progressive multifocal leukoencephalopathy during treatment with the monoclonal antibody ofatumumab. Takahisa Tateishi, MD, PhD, of the Japan Community Health Care Organization Kyushu Hospital, and colleagues suggested ofatumumab therapy may be associated with developing this neurologic disorder.
“Progressive multifocal leukoencephalopathy is a rare and severe demyelinating disease of the brain caused by [the] reactivation of John Cunningham virus (JCV) in patients with HIV or people who have received monoclonal antibody therapy,” the investigators commented. “The reactivation of JCV is thought to be involved in the hypothesis that the decline in cell-mediated immunity caused by the decrease in cytotoxic T lymphocytes leads to uncontrollable JCV proliferation.”
In this case report, the patient presented with cognitive impairment and visual-field defects during ofatumumab therapy for refractory CLL. An MRI showed T1-weighted low-intensity and T2-weighted high-intensity lesions with patchy gadolinium enhancement in the subcortical white matter of the right parietal and left frontotemporal lobes. After JCV DNA was detected in his cerebrospinal fluid, the patient was diagnosed with progressive multifocal leukoencephalopathy. The levels of JCV DNA seemed to decrease after plasma exchange and administration of the antidepressant mirtazapine and the antimalaria drug mefloquine; however, 55 days after treatment initiation, the patient died of a bacterial infection in an immunocompromised state.
“Many clinical trials and studies of other monoclonal antibodies…are seeking to expand the indications of these treatments from oncology to neurology,” the investigators remarked. Thus, healthcare professionals prescribing these agents should be aware of all potentially severe adverse reactions to them.
Disclosure: The study authors reported no conflicts of interest.
