Progressive multifocal leukoencephalopathy (PML) after first-line, single agent ibrutinib therapy in a patient with chronic lymphocytic leukemia (CLL): a case report and literature review

Progressive Multifocal Leukoencephalopathy (PML) is a rare but often fatal opportunistic infection caused by the John Cunningham ("JC") virus in immunocompromised individuals. PML is usually described after multiple lines of immunochemotherapy often containing rituximab in patients with B-cell malignancies including chronic lymphocytic leukemia (CLL). The occurrence of PML after single agent ibrutinib for the treatment of CLL is extremely rare. We report a case of PML presented shortly after ibrutinib was initiated as the first-line monotherapy for the treatment of a patient with CLL. The patient presented with rapidly progressive neurologic symptoms that started two weeks after ibrutinib was started. An MRI of the brain was concerningfor PML, but multiple CSF samples tested negative using a polymerase chain reaction for the JC virus. Finally, a brain biopsy clinched the diagnosis of PML. Unfortunately, the patient deteriorated over the next several weeks despite the discontinuation of ibrutinib and died from the PML. As ibrutinib has been moved up to the frontline setting for the treatment of CLL, it is important to increase awareness of the association of ibrutinib therapy to the occurrence of PML. The prognosis of PML remains poor despite a prompt diagnosis and the withdrawal of ibrutinib to allow immune reconstitution.