Progressive Multifocal Leukoencephalopathy during Ixazomib-Based Chemotherapy

Abstract

Progressive multifocal leukoencephalopathy (pml) is a rare demyelinating disease of the central nervous system that most often affects immunocompromised individuals. It is caused by the reactivation of the John Cunningham virus (jcv), which is found in latent form in the majority of adults. We describe a 59-year-old man with multiple myeloma who developed severe neurological deficits during treatment with ixazomib-based chemotherapy. A diagnosis of pml was established with gadolinium-enhanced magnetic resonance imaging (mri) and by detection of jcv in the cerebrospinal fluid. Despite cessation of chemotherapy and treatment with mirtazapine, he had an inexorable neurological decline and died two months after presenting to hospital. Multiple myeloma and its treatments can predispose patients to opportunistic infections including pml. Although there have been case reports of pml in patients with multiple myeloma treated with bortezomib (a different proteosome inhibitor), this is, to our knowledge, the first documented case of pml in a patient treated with a regimen that includes ixazomib.

164 Progressive multifocal leukoencephalopathy (PML) following autologous periph- eral blood stem cell transplantation for multiple myeloma

“…24 Developing PML after MM is rare with 11 case reports in the literature. [25][26][27][28][29][30][31][32][33][34][35] Presentations varied in these patients depending on the location of the lesion and included: hemiparesis and hemiplegia, 25,28,29,32,35 numbness and tingling of the legs, 29 rapid cognitive decline, 25,27,33 homonymous hemianopia, 27 ataxia, 27 speech difficulties, 26,[30][31][32]35 incontinence, 26 apathy, 29 and memory impairment. 32-34. Trying to identify if an individual aspect of the MM treatment was responsible for the development of PML is difficult from these isolated case studies.…”

Progressive multifocal leukoencephalopathy following five lines of therapy and three autologous bone marrow transplants for multiple myeloma

“…Many patients receive immunomodulator therapy(ies), with responses often consolidated with an autologous SCT 17. Cases of PML following the use of lenalidomide, dexamethasone, cyclophosphamide and the newer proteasome inhibitor ixazomib have all been reported 18–21. These cases highlight the importance of monitoring for neurological signs and symptoms in patients on immunomodulating drugs with early consideration given to PML.…”

Progressive multifocal leukoencephalopathy in the context of newer therapies in hematology and review of new treatment strategies

“…There has been only one case reporting the emergence of PML in a patient treated with ixazomib-based therapy. 47…”

“…Ixazomib and carfilzomib are novel proteasome inhibitors also used in MM. There has been only one case reporting the emergence of PML in a patient treated with ixazomib‐based therapy 47 …”