Smoldering Multiple Myeloma Associated Leukoencephalopathy Presenting with Holmes Tremor, Ataxia, and Pyramidal Syndrome

Aquino, Camila C.; Connolly, Barbara S.; Lang, Anthony E.

doi:10.1002/mdc3.12623

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…The presentation of leukoencephalopathy with demyelinating processes among patients with MM who are receiving active treatment generally prompts a differential diagnosis that includes meningoencephalitis, malignant CNS involvement, PML, posterior reversible encephalopathy syndrome (PRES), genetic leukodystrophy, and chemotherapy-induced leukoencephalopathy. [4][5][6][11][12][13] For the patients in our series, we ruled out infection and malignant cerebral involvement because of negative CSF results throughout their courses of therapy. A summary of the cases is presented in Table 1 with patient timelines in Figure 2.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In the setting of multiple myeloma (MM), leukoencephalopathy is rare and has been predominantly documented secondary to central nervous system (CNS) disease, paraneoplastic syndrome, infectious processes, genetic conditions, and medication use. [3][4][5][6] Leukoencephalopathy-primarily John Cunningham (JC) virus-associated progressive multifocal leukoencephalopathy (PML)-has been reported in association with monoclonal antibody treatment. 7 Daratumumab is a human monoclonal antibody that targets CD38, a cell surface glycoprotein that is highly expressed on myeloma cells.…”

Section: Introductionmentioning

confidence: 99%

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Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma

Kareem¹,

Viswanathan²,

Sahebjam³

et al. 2022

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Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.

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