Concurrent progressive multifocal leukoencephalopathy and central nervous system infiltration by multiple myeloma: A case report

Abstract

Progressive multifocal leukoencephalopathy rarely occurs in patients with multiple myeloma. Intracranial central nervous system invasion is also an uncommon event in multiple myeloma, occurring in less than 1% of cases. We describe herein an exceptional case of coexisting progressive multifocal leukoencephalopathy and intraparenchymal central nervous system myeloma infiltration. A 73-year-old woman with relapsed multiple myeloma was treated with 15 cycles of lenalidomide and dexamethasone, but therapy had to be stopped because of a hip fracture after a fall. During hospitalization, the patient developed progressive multifocal leukoencephalopathy caused by John Cunningham virus, and a prominent intra-parenchymal CD138-positive infiltrate was detected. VDJ rearrangements of the immunoglobulin heavy chain gene and the mutational profile of plasma cells in bone marrow at the time of diagnosis and in brain biopsy after progression were analyzed by next generation sequencing, showing genetic differences between medullary and extramedullary myeloma cells. The role of long-term treatment with lenalidomide and dexamethasone in the development progressive multifocal leukoencephalopathy or intraparenchymal central nervous system myeloma infiltration remains unknown. However, our results suggest that both events may have arisen as a consequence of treatment-related immunosuppression. Thus, an appropriate clinical approach compatible with the simultaneous treatment of progressive multifocal leukoencephalopathy and multiple myeloma should be developed.

Multiple myeloma with central nervous system relapse

“…Multiple myeloma with CNS involvement develops via hematogenous dissemination of malignant cells or contiguous spread of the tumor, often associated with PCL and cranial plasmacytoma, respectively. 1,15 Although it has been suggested that invasion of the CNS is enabled by treatment of MM with immunomodulatory drugs (IMiD), with a report of an MM patient receiving lenalidomide prior to CNS-MM progression, 17 this is not robust evidence. Data for EMD in general suggest that escape from the BM is enabled by mutations to tumor suppressor genes such as TP53, oncogenes such as RAS, and altered expression of adhesion molecules, as outlined above.…”

Progressive multifocal leukoencephalopathy

“…Although large cohorts of patients with PML in the setting of natalizumab have been described, 17,18 most of the literature on diverse etiologies of PML in recent decades has been limited to small case series and individual reports, which are subject to publication bias based on either unexpectedly favorable or unfavorable outcomes. 19,20 With the new promise of effective therapy for this devastating disease, understanding the diverse presentations of PML is increasingly important because early manifestations may be difficult to recognize but are most amenable to treatment. Here, we report the risk factors and outcomes in a cohort of patients diagnosed with PML and followed at 2 tertiary care hospitals in the United States over a 25-year period.…”

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.…”