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The case describes a 66-year-old woman with heavily pretreated IgG kappa multiple myeloma receiving sequential anti-BCMA×CD3 and anti-GPRC5D×CD3 BiAb therapy, who developed both BK polyomavirus-associated nephropathy and rapidly fatal progressive multifocal leukoencephalopathy. Longitudinal multi-modal immunophenotyping and functional assays showed loss of humoral and virus-specific cellular immunity. Diagnosis was confirmed by PCR of plasma and cerebrospinal fluid for BKV and JCV, and by autopsy immunohistochemistry identifying SV40 large T antigen.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/progressive-multifocal-leukoencephalopathy-and-bk-virus-nephropathy-with-bispecific-antibody-therapy-in-multiple-myeloma-case-report/448235/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/progressive-multifocal-leukoencephalopathy-and-bk-virus-nephropathy-with-bispecific-antibody-therapy-in-multiple-myeloma-case-report/448235.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-05","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What treatment sequence was used in this multiple myeloma patient?","Question",{"text":112,"@type":113},"The patient received sequential bispecific antibody therapy with anti-BCMA×CD3 for salvage treatment after her seventh relapse, followed by anti-GPRC5D×CD3 when she later progressed.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were progressive multifocal leukoencephalopathy and BK virus nephropathy diagnosed?",{"text":117,"@type":113},"PML was confirmed by MRI findings plus marked elevation of BKV and JCV by PCR in plasma and cerebrospinal fluid. Renal biopsy demonstrated BKV-associated nephropathy with immunohistochemistry consistent with viral involvement.",{"name":119,"@type":110,"acceptedAnswer":120},"What immunologic changes were observed during the disease course?",{"text":121,"@type":113},"Humoral responses declined, including a marked decrease in antibodies against SV40 small t antigen and other viral antigens. Cellular immunity also decreased, with reduced CD4+ and CD8+ T-cell and NK/B-cell subpopulations and diminished CD8+ T-cell recall responses after peptide stimulation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},448235,1791127790,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","CASE REPORT  \nProgressive multifocal leukoencephalopathy and BK virus-nephropathy with bispecific antibody therapy in multiple myeloma  \nT-cell redirecting therapies have dramatically altered the treatment landscape of multiple myeloma (MM) . Bispecific antibodies (BiAb) have been shown to induce deep and durable responses in MM, even in those with heavily pre-treated disease. Despite their efficacy, there is a significant risk of infection, with severe (grade 3 or higher) infectious complications occurring in up to 45% of MM patients treated with BiAb 1 Here we describe a unique case of a patient with MM treated sequentially with anti-BCMAx CD3 and anti-GPRC5D x CD3 BiAb who developed both renal failure from BK polyomavirus 1 (BKV) associated nephropathy and rapidly fatal neurologic decline due to progressive multifocal leukoencephalopathy (PML), with loss of both humoral and virus-specific cellular immunity, clearly demonstrable by longitudinal multi-modal immunophenotyping and functional assays.  \nWe present a 66-year-old female with heavily treated IgG kappa MM who received an anti-BCMA x CD3 BiAb for salvage therapy after her seventh relapse. She progressed after two years of therapy and shortly thereafter developed progressive renal dysfunction (Figure 1A, B), whose etiology was initially ascribed to MM progression. She was treated with chemotherapy (dexamethasone, cyclophosphamide, etoposide and cisplatin, then bendamustine and bortezomib) and ultimately started on anti-GPRC5Dx CD3 BiAb therapy. She responded rapidly to therapy but had persistent decline in renal function and a renal biopsy was performed, which demonstrated BKV-associated nephropathy, an entity more commonly seen in solid organ transplant recipients (Figure 1C) . Approximately two months later, she developed progressive decline in mental status, initially with confusion, then ultimately became less responsive, requiring hospitalization. She subsequently required intubation for airway protection, and MRI was notable for new white matter hyperintensities in the temporal and occipital lobes, consistent with PML, a rare and devastating demyelinating disease of the central nervous system caused by the reactivation of the JC polyomavirus 2 (JCV) in the setting of severe immunosuppression (Figure 1D) . Plasma showed marked elevation of BKV and JCV by PCR (BKV 9.9 million copies/mL, JCV 15,600 copies/mL) as did the cerebrospinal fluid (BKV 54,700 copies/mL, JCV 120,000 copies/mL), confirming the diagnosis of PML. The patient developed status epilepticus and died shortly thereafter. An autopsy was performed with the family’s consent, which confirmed demyelination and viral inclusions in the brain by immunohistochemis-  \ntry for Simian Virus 40 (SV40) large T antigen (Ag), a key polyomavirus protein involved in viral transformation of host cells (Figure 1E) .2  \nTo assay humoral protection against BKV and JCV, we used a multiplexed in-solution protein array (MISPA) platform, which uses a protein-antigen library to evaluate and compare serologies of a large scale of samples to hundreds of Ag simultaneously (Figure 2A) .3 This platform includes the SV40 small t Ag, which shares sequence homology with BKV and JCV.4 Polyomavirus small t Ag are thought to assist in viral replication via transregulatory activity on promoters transcribed by RNA polymerases II and III.5 We collected longitudinal serum samples from our patient, under Multiple Myeloma Biorepository IRB Study ID 18- 00456 (approval date 04/26/2024), and analyzed five of these samples while on anti-BCMA x CD3 BiAb therapy via the MISPA platform. We compared the antibody levels of our patient to those of healthy controls (N=100) . Notably, there was a significant decrease in antibody levels against SV40 small t Ag when compared to healthy controls. Similarly, a decrease in antibody response was also seen to other viral Ag, including various COVID and seasonal coronavirus Ag (Figure 2B) . It is interesting to ","cbCaipdEUSm0Aiu3","https://ap.wps.com/l/cbCaipdEUSm0Aiu3","pdf",1430821,"English","# Case report\n## Treatment course and clinical deterioration\n## Diagnostic confirmation of PML and BKV nephropathy\n## Humoral immunity assessment with MISPA\n## Cellular immunity profiling and T-cell functional assays","[{\"question\":\"What treatment sequence was used in this multiple myeloma patient?\",\"answer\":\"The patient received sequential bispecific antibody therapy with anti-BCMA×CD3 for salvage treatment after her seventh relapse, followed by anti-GPRC5D×CD3 when she later progressed.\"},{\"question\":\"How were progressive multifocal leukoencephalopathy and BK virus nephropathy diagnosed?\",\"answer\":\"PML was confirmed by MRI findings plus marked elevation of BKV and JCV by PCR in plasma and cerebrospinal fluid. Renal biopsy demonstrated BKV-associated nephropathy with immunohistochemistry consistent with viral involvement.\"},{\"question\":\"What immunologic changes were observed during the disease course?\",\"answer\":\"Humoral responses declined, including a marked decrease in antibodies against SV40 small t antigen and other viral antigens. Cellular immunity also decreased, with reduced CD4+ and CD8+ T-cell and NK/B-cell subpopulations and diminished CD8+ T-cell recall responses after peptide stimulation.\"}]","Progressive multifocal leukoencephalopathy and BK virus-nephropathy with bispecific antibody therapy in multiple myeloma - Case report | PDF",1790726178,13]