Progressive Multifocal Leukoencephalopathy Among Ibrutinib Treatment In Chronic Lymphocytic Leukemia.

Abstract

Both chronic lymphocytic leukemia (CLL) itself and the drugs used for its treatment, pose a risk for progressive multifocal leukoencephalopathy (PML). Although the relationship between Rituximab and PML is well known, case reports that have been recently published, suggest that ibrutinib; which is used in the treatment of CLL, may increase the risk of PML. Here, we report a case of 64 year-old female patient with CLL who was previously treated with rituximab, fludarabine and bendamustin but developed PML after receiving monotherapy with ibrutinib. According to Naranjo's algorithm, the causality relationship with the drug is possible with a score of 3. The patient initially exhibited neurological symptoms. Magnetic resonance of the brain revealed a bilateral asymmetric hyperintensity in the white matter involving the parietal and occipital lobules, and there was no mass effect, edema, hemorrhagic or iscemic lesions. No enhancement of contrast media was observed. The findings were consistent with demyelination and suggestive of PML. Mirtazapine treatment was initiated. However, neurological sympthoms continuously progressed over the following weeks and the patient, aged 64, died six weeks after diagnosis of PML. PML is a rare and often fatal demyelinating disease of the central nervous system (CNS) that is exclusively seen in immunocompromised patients and there is no specific agent to treat PML. The case discussed here, highlights that the use of ibrutinib in chronic lymphocytic leukemia (CLL) therapy may result in PML.