Lenalidomide-related Progressive Multifocal Leukoencephalopathy: A Case Report and Review of Drug-related Cases in Multiple Myeloma

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder caused by reactivation of John Cunningham virus. Prolonged treatment with immunosuppressive therapy is a risk factor for the development of PML, and cases have already been linked to agents used in the treatment of lymphopro-liferative disorders such as rituximab, fludarabine, and brentuximab. However, literature on the epidemiology of PML in the multiple myeloma (MM) population and the risk associated with immunomodulatory agents or proteasome inhibitors is lacking. We present a case of PML in a 60-year-old female with immunoglobulin G MM on lenalidomide/dexamethasone for progressive disease post-autologous stem cell transplantation and discuss the causation, diagnosis, and management of PML in MM in the context of previous published reports. This report highlights the importance of considering PML in patients with MM who develop focal neurologic deficits. This is critical as early detection with cessation of causative chemotherapy is the only effective management strategy, yet it must be balanced against the risks of losing myeloma disease control. Such vigilance should not be limited to patients on immunomodulatory agents as our review identified cases linked to other drug classes including proteasome inhibitors. It should also be extended to newer agents, which are yet to be implicated, such as monoclonal antibodies.