Abstract
Progressive multifocal leukoencephalopathy (PML) is a potentially fatal demyelinating disease of the central nervous system caused by reactivation of the John Cunningham virus (JCV) and occurs mainly in immunocompromised patients with lymphoproliferative and myeloproliferative disorders, human immunodeficiency virus (HIV) infection or immunomodulatory therapy. The aim of this article is to present the atypical case of a 72-year-old woman with IgG-kappa multiple myeloma (MM) treated with DRD (D: daratumumab; R: lenalidomide; D: dexamethasone), who was admitted to our neurology department in August 2023 after developing left hemiparesis and gait disorder within a few weeks after 2 years of treatment. A preliminary brain magnetic resonance imaging (MRI) revealed the presence of multiple hyperintense white matter lesions on fluid attenuated inversion recovery (FLAIR), with a predilection for the cerebellum, brainstem bridge and right temporal lobe. Despite a comprehensive workup that included an initial lumbar puncture, the precise etiology of the lesions remained elusive. Clinical improvement enabled the patient to be discharged home, but she was subsequently readmitted to the hospital due to the onset of a major cerebellar syndrome. An increase in leukopathy was demonstrated on cerebral MRI, with a particular focus on the cerebellar region. Suspecting PML, a second lumbar puncture was performed and the polymerase chain reaction (PCR) was positive for JCV. Sadly, despite the administration of an experimental therapy, the patient died within weeks of diagnosis. The literature reports several cases of PML associated with therapies used in MM, including lenalidomide and daratumumab. However, to the best of our knowledge, only one case has been described under the DRD regimen by Seko et al. In conclusion, it is crucial to increase clinical surveillance in patients receiving DRD therapy in order to promptly identify any potential neurological deterioration. Furthermore, it is vital to screen for the possibility of PML, an extremely rare but serious complication of this treatment, and to promptly discontinue the therapy in the event of its occurrence.