Progressive Multifocal Leukoencephalopathy following Daratumumab therapy for refractory Multiple Myeloma – a case report

Abstract

Context: PML is a dymyeliniating disease of the brain, caused by JC virus infection reactivation in immunocompromised patients, especially by AIDS, hematological disease and immunosuppressive therapies. Case report: A 67-year-old woman was diagnosed with multiple myeloma (MM) in 2018 and use of bortezomib/cyclophosphamide/dexamethasone and thalidomide was ineffective. She underwent treatment with monthly daratumumab starting in January 2020. After one year, she experienced progressive amnesia, apathy and confusion. At admission, examination revealed apathy, monosyllabic communication and frontal release, progressing to mutism and abulia. T2 FLAIR-weighted MRI of the brain performed in March 2021 showed a hyperintense non-enhancing lesion affecting thalamus, internal capsule, lentiform and deep white matter of left lobes. MRI performed one month before symptoms onset showed a small lesion in subinsular region – indicating incipient involvement. Cerebrospinal fluid PCR was positive for JC viruses, and PML was diagnosed. Conclusions: This report proves that concomitant hematologic and drug- immunocompromised patients presenting with neurological symptoms should be investigated for PML. There are few reports in the literature of PML occurring in MM, especially after use of daratumumab, an anti-CD38 monoclonal antibody. Recently, one small case series demonstrated some improvement in pembrolizumab (a checkpoint inhibitor)-treated PML, but no routinely therapy is recommended. Understanding severity of both disease, patient was discharged receiving conservative treatment.