PMC10192558_01
Treatment timeline of multiple myeloma-specific therapies from disease onset until the diagnosis of PML. HDT, high dose therapy. *Nine series without cyclophosphamide.
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F1
Treatment before the fourth ASCT, in 2016, was bortezomib, thalidomide, and dexamethasone followed by high-dose melphalan (Figure 1).
Evolution of progressive multifocal leukoencephalopathy (PML) and magnetic resonance imaging (MRI) changes. (A-C) First brain MRI with fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI) b 1,000 images, and the apparent diffusion coefficient (ADC) map presented from left to right columns showing a lesion of the splenium of the corpus callosum, predominantly on the right side of the increased signal on FLAIR and DWI b 1,000 images, without restricted diffusion on the ADC map. (D-F) Second brain MRI with FLAIR and DWI b 1,000 images, as well as the ADC map, presented from left to right columns indicating an increase in the size of the corpus callosum lesion along with partial peripheral restricted diffusion visible on the DWI b 1,000 images and ADC map (yellow arrows). The newly appearing peripheral changes on diffusion images were indicative of PML. (G, H) FLAIR images of the second brain MRI demonstrating new lesions in the right temporal lobe and left parietal lobe (white arrows). (I) Susceptibility-weighted image of the second brain MRI without cortical-subcortical junction band of low signal intensity related to the expanding lesion from the corpus callosum (dotted circle). These susceptibility brain changes, which most likely represent iron accumulation, were described only in a part of PML patients.
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F2
Brain MRI showed no intracranial myeloma-related findings, but a non-specific lesion involving the splenium of the corpus callosum that could possibly represent a subacute ischemic change, a cytotoxic lesion of the corpus callosum, or a low-grade glioma was described (Figures 2A-C). This led to a new brain MRI, performed 12 weeks after the first brain MRI, showing progression of the corpus callosum lesion along with new brain lesions (Figures 2D-I).
Frequency of specific multiple myeloma therapies in cases that developed progressive multifocal leukoencephalopathy. Data are from the United States Food and Drug Administration adverse events reporting system database. MAB, monoclonal antibodies; IMID, immunomodulatory drugs; PI, proteasome inhibitors; ACA, alkylating agents; TI, topoisomerase inhibitors; OCA, other cytostatic agents; OI, other immunosuppressive agents.
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F3
Reported MM-specific therapies in patients with PML from the FAERS database are depicted in Figure 3.