Progressive Multifocal Leukoencephalopathy in Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study

Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy modality that has shown remarkable response rates in refractory hematologic malignancies, including multiple myeloma (MM). Cytokine release syndrome (CRS) and neurotoxicity are well-described side effects of this therapy. CAR T-cell therapy recipients are also at increased risk for infections due to immune dysfunction, history of multiple lines of therapy, history of lymphodepleting chemotherapy prior to cell infusion, and prolonged B-cell aplasia. Progressive multifocal leukoencephalopathy (PML) is an opportunistic disease of the central nervous system caused by the reactivation of JC virus (JCV) in the setting of immunosuppression, which leads to increased morbidity and mortality. Here, we present a patient treated with ciltacabtagene autoleucel for refractory MM who presented with PML around 2 months after receiving CAR T-cell therapy. This case emphasizes the risks for the development of PML in immunocompromised patients potentially related to persistent B-cell aplasia, hypogammaglobulinemia, and prolonged immunosuppression and discusses treatment approaches. Treatments for PML are mostly focused on reconstituting immunity. However, no adequate treatment strategy for PML has yet been established and further research is needed.