[Targeted therapy and progressive multifocal leukoencephalopathy (PML): PML in the era of monoclonal antibody therapies]

Abstract

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system and is associated with John Cunningham (JC) virus infection in the oligodendrocytes. The number of patients with PML increased after the pandemic of acquired immunodeficiency syndrome. Thereafter, an association between PML and monoclonal antibody therapy has come into light. Thus far, several monoclonal antibodies have been reported to cause PML. Currently, according to the Barts and the London School of Medicine and Dentistry, the number of PML cases due to natalizumab treatment for multiple sclerosis is 395 (incidence is 3.28/1,000). Moreover, the number of individuals with PML due to rituximab treatment is increasing (over 100 cases). Efalizumab, infliximab, adalimumab, etanercept, ibritumomab tiuxetan, bevacizumab, alemtuzumab, cetuximab, and brentuximab are also reported as risk factors of PML. The diagnosis of PML is based on clinical, neuroradiological, pathological, and molecular analyses. In clinical setting, magnetic resonance imaging provides the most important information in the diagnosis of PML. Patients with PML due to monoclonal antibody treatment may present clinical symptoms different from that of the classic PML, such as sensory disturbance and seizure. Once PML is identified in an individual receiving monoclonal antibody therapy, the monoclonal antibody must be immediately discontinued and removed from the body by plasmapheresis. Because most patients may present immune reconstitution inflammatory syndrome (IRIS), steroid therapy must be considered immediately. However, the prognosis of PML is still worse in patients receiving monoclonal antibody therapy. To prevent PML development, sophisticated and well-organized strategies must be established for monoclonal antibody treatment. Besides neurologists, physicians from other fields must be aware of PML associated with resulted from monoclonal antibody therapy.