A Case of Progressive Multifocal Leukoencephalopathy Caused by Epcoritamab.

A female patient aged in her 50s had presented with the onset of follicular lymphoma (FL) with left mandibular swelling, with a pathological grade of 1 and clinical stage of Ⅳ (Ann Arbor staging). Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP) resulted in complete molecular remission (CMR). The patient experienced two recurrences, and treatments were successful; however, the side effect of continuous lymphocytopenia existed eight years after the onset. For the third recurrence of FL, weekly epcoritamab therapy was administered with a white blood cell count of 2,010 /μL with neutrophils of 1,240/μL, lymphocytes of 430/μL, red blood cells of 390 × 10/μL, and platelets of 17.8 × 10/μL. Fludeoxyglucose positron emission tomography (FDG-PET) confirmed CMR after six cycles of epcoritamab. After the 11th epcoritamab, the patient was diagnosed with progressive multifocal leukoencephalopathy (PML), presenting significant left hemispatial neglect and visuospatial problems. Brain magnetic resonance imaging of fluid-attenuated inversion recovery and diffusion-weighted imaging showed high intensity in the right parietotemporal subcortex and frontal subcortical lesion with high or iso intensity on the apparent diffusion coefficient. FDG-PET did not show lymphoma recurrence. The patient had white blood cells of 2,310 /μL with lymphocytes of 480/μL, CD4-positive lymphocytes of 124/μL, and CD8-positive lymphocytes of 153/μL. The JC virus (JCV) deoxyribonucleic acid (DNA) level in cerebrospinal fluid (CSF) as examined by polymerase chain reaction (PCR) increased to 1.466 × 10 copies/mL. The patient became unconscious and died three months after diagnosis of PML. We report the first case of PML as a complication of epcoritamab, a bispecific antibody targeting CD3 and CD20 that redirects and activates T cells, which is expected to be used for treating FL. PML is a fatal infection of the central nervous system without effective treatment caused by the reactivation of the JCV in immunodeficient hosts. The antibody test for JCV is recommended for patients with multiple sclerosis for an earlier diagnosis, which is not common in other diseases. We should be aware of PML through innovative therapy.