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CAR T-cell therapy rescues adolescent with rapidly progressive lupus nephritis from haemodialysis
Morbidity and mortality in juvenile-onset systemic lupus erythematosus are higher than adult-onset disease, and children with lupus nephritis have higher scores on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).2,3 End-stage renal disease and permanent haemodialysis are severe adve...
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Published in: | The Lancet (British edition) 2024-04, Vol.403 (10437), p.1627-1630 |
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creator | Krickau, Tobias Naumann-Bartsch, Nora Aigner, Michael Kharboutli, Soraya Kretschmann, Sascha Spoerl, Silvia Vasova, Ingrid Völkl, Simon Woelfle, Joachim Mackensen, Andreas Schett, Georg Metzler, Markus Müller, Fabian |
description | Morbidity and mortality in juvenile-onset systemic lupus erythematosus are higher than adult-onset disease, and children with lupus nephritis have higher scores on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).2,3 End-stage renal disease and permanent haemodialysis are severe adverse events than can occur due to juvenile-onset and adult-onset systemic lupus erythematosus, with 15% of all patients with lupus nephritis developing end-stage renal disease.4 The therapeutic goal of complete remission of lupus nephritis is only reached in 60% of patients by conventional therapies, including immunosuppressive drugs and B-cell-depleting antibodies,3 and two-thirds of adults with juvenile-onset systemic lupus erythematosus develop organ damage and impaired health-related quality of life without reaching drug-free remission.5 Due to their high B-cell depletion activity, CD19-targeted chimeric antigen receptor (CAR) T cells are a potentially powerful strategy to treat autoimmune diseases, such as systemic lupus erythematosus.6,7 In a small case series of eight patients aged 18–38 years with treatment-refractory systemic lupus erythematosus, adoptive transfer of CD19-targeted CAR T cells induced a deep reset of B cells leading to abrogation of autoreactive antibodies and durable remission, including abrogation of lupus nephritis with a follow-up time of 6–29 months.8 Herein, we report on a 15-year-old female patient with severe and rapidly progressive systemic lupus erythematosus. Low levels of complement and presence of several autoantibodies including anti-nuclear-antibody anti-double-stranded DNA (anti-dsDNA; 4545 IU/mL [normal range is |
doi_str_mv | 10.1016/S0140-6736(24)00424-0 |
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Low levels of complement and presence of several autoantibodies including anti-nuclear-antibody anti-double-stranded DNA (anti-dsDNA; 4545 IU/mL [normal range is <100 IU/mL]), anti-nucleosome, and anti-histone antibodies were evident. Because renal function further rapidly worsened under therapy escalation with high-dose methylprednisolone and cyclophosphamide, plasma separation was initiated, leading to a reduction in autoantibody levels. At our site (University Hospital Erlangen, Erlangen, Germany), we initiated CD19-targeted CAR T-cell therapy in an expanded access programme for critically ill patients according to the German Arzneimittelgesetz, §21/2 and the Arzneimittel-Härtefall-Verordnung §2 following a mandatory case review by an independent interdisciplinary board. Despite kidney failure, CAR T-cell therapy was safe and well tolerated due to appropriate dose adjustment of lymphodepletion.</description><identifier>ISSN: 0140-6736</identifier><identifier>ISSN: 1474-547X</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(24)00424-0</identifier><identifier>PMID: 38642568</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adolescent ; Adolescents ; Adoptive transfer ; Adults ; Anti-DNA antibodies ; Antibodies ; Antihypertensives ; Arthritis ; Autoantibodies ; Autoimmune diseases ; CD19 antigen ; Cell therapy ; Chimeric antigen receptors ; Chronic conditions ; Creatinine ; Cyclophosphamide ; Cytokine storm ; Depletion ; Disease Progression ; Drug dosages ; End-stage renal disease ; Female ; Hematuria ; Hemodialysis ; Histones ; Humans ; Hypertension ; Immunosuppressive agents ; Immunotherapy, Adoptive - methods ; Kidney diseases ; Lupus ; Lupus nephritis ; Lupus Nephritis - therapy ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Male ; Methylprednisolone ; Morbidity ; Nephritis ; Patients ; Pediatrics ; Quality of life ; Receptors, Chimeric Antigen ; Remission ; Remission (Medicine) ; Renal Dialysis ; Renal failure ; Renal function ; Systemic lupus erythematosus ; Therapy</subject><ispartof>The Lancet (British edition), 2024-04, Vol.403 (10437), p.1627-1630</ispartof><rights>2024 Elsevier Ltd</rights><rights>2024. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3550-d27bb7a52d6553bf379e6361b9e2c3a8b1e68512c5e2af9c58f5acab21d7e7b43</citedby><cites>FETCH-LOGICAL-c3550-d27bb7a52d6553bf379e6361b9e2c3a8b1e68512c5e2af9c58f5acab21d7e7b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38642568$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krickau, Tobias</creatorcontrib><creatorcontrib>Naumann-Bartsch, Nora</creatorcontrib><creatorcontrib>Aigner, Michael</creatorcontrib><creatorcontrib>Kharboutli, Soraya</creatorcontrib><creatorcontrib>Kretschmann, Sascha</creatorcontrib><creatorcontrib>Spoerl, Silvia</creatorcontrib><creatorcontrib>Vasova, Ingrid</creatorcontrib><creatorcontrib>Völkl, Simon</creatorcontrib><creatorcontrib>Woelfle, Joachim</creatorcontrib><creatorcontrib>Mackensen, Andreas</creatorcontrib><creatorcontrib>Schett, Georg</creatorcontrib><creatorcontrib>Metzler, Markus</creatorcontrib><creatorcontrib>Müller, Fabian</creatorcontrib><title>CAR T-cell therapy rescues adolescent with rapidly progressive lupus nephritis from haemodialysis</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Morbidity and mortality in juvenile-onset systemic lupus erythematosus are higher than adult-onset disease, and children with lupus nephritis have higher scores on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).2,3 End-stage renal disease and permanent haemodialysis are severe adverse events than can occur due to juvenile-onset and adult-onset systemic lupus erythematosus, with 15% of all patients with lupus nephritis developing end-stage renal disease.4 The therapeutic goal of complete remission of lupus nephritis is only reached in 60% of patients by conventional therapies, including immunosuppressive drugs and B-cell-depleting antibodies,3 and two-thirds of adults with juvenile-onset systemic lupus erythematosus develop organ damage and impaired health-related quality of life without reaching drug-free remission.5 Due to their high B-cell depletion activity, CD19-targeted chimeric antigen receptor (CAR) T cells are a potentially powerful strategy to treat autoimmune diseases, such as systemic lupus erythematosus.6,7 In a small case series of eight patients aged 18–38 years with treatment-refractory systemic lupus erythematosus, adoptive transfer of CD19-targeted CAR T cells induced a deep reset of B cells leading to abrogation of autoreactive antibodies and durable remission, including abrogation of lupus nephritis with a follow-up time of 6–29 months.8 Herein, we report on a 15-year-old female patient with severe and rapidly progressive systemic lupus erythematosus. Low levels of complement and presence of several autoantibodies including anti-nuclear-antibody anti-double-stranded DNA (anti-dsDNA; 4545 IU/mL [normal range is <100 IU/mL]), anti-nucleosome, and anti-histone antibodies were evident. Because renal function further rapidly worsened under therapy escalation with high-dose methylprednisolone and cyclophosphamide, plasma separation was initiated, leading to a reduction in autoantibody levels. At our site (University Hospital Erlangen, Erlangen, Germany), we initiated CD19-targeted CAR T-cell therapy in an expanded access programme for critically ill patients according to the German Arzneimittelgesetz, §21/2 and the Arzneimittel-Härtefall-Verordnung §2 following a mandatory case review by an independent interdisciplinary board. Despite kidney failure, CAR T-cell therapy was safe and well tolerated due to appropriate dose adjustment of lymphodepletion.</description><subject>Adolescent</subject><subject>Adolescents</subject><subject>Adoptive transfer</subject><subject>Adults</subject><subject>Anti-DNA antibodies</subject><subject>Antibodies</subject><subject>Antihypertensives</subject><subject>Arthritis</subject><subject>Autoantibodies</subject><subject>Autoimmune diseases</subject><subject>CD19 antigen</subject><subject>Cell therapy</subject><subject>Chimeric antigen receptors</subject><subject>Chronic conditions</subject><subject>Creatinine</subject><subject>Cyclophosphamide</subject><subject>Cytokine storm</subject><subject>Depletion</subject><subject>Disease Progression</subject><subject>Drug dosages</subject><subject>End-stage renal disease</subject><subject>Female</subject><subject>Hematuria</subject><subject>Hemodialysis</subject><subject>Histones</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Immunosuppressive agents</subject><subject>Immunotherapy, Adoptive - methods</subject><subject>Kidney diseases</subject><subject>Lupus</subject><subject>Lupus nephritis</subject><subject>Lupus Nephritis - therapy</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Methylprednisolone</subject><subject>Morbidity</subject><subject>Nephritis</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Quality of life</subject><subject>Receptors, Chimeric Antigen</subject><subject>Remission</subject><subject>Remission (Medicine)</subject><subject>Renal Dialysis</subject><subject>Renal failure</subject><subject>Renal function</subject><subject>Systemic lupus 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T-cell therapy rescues adolescent with rapidly progressive lupus nephritis from haemodialysis</title><author>Krickau, Tobias ; Naumann-Bartsch, Nora ; Aigner, Michael ; Kharboutli, Soraya ; Kretschmann, Sascha ; Spoerl, Silvia ; Vasova, Ingrid ; Völkl, Simon ; Woelfle, Joachim ; Mackensen, Andreas ; Schett, Georg ; Metzler, Markus ; Müller, Fabian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3550-d27bb7a52d6553bf379e6361b9e2c3a8b1e68512c5e2af9c58f5acab21d7e7b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Adolescents</topic><topic>Adoptive transfer</topic><topic>Adults</topic><topic>Anti-DNA antibodies</topic><topic>Antibodies</topic><topic>Antihypertensives</topic><topic>Arthritis</topic><topic>Autoantibodies</topic><topic>Autoimmune diseases</topic><topic>CD19 antigen</topic><topic>Cell therapy</topic><topic>Chimeric antigen receptors</topic><topic>Chronic conditions</topic><topic>Creatinine</topic><topic>Cyclophosphamide</topic><topic>Cytokine storm</topic><topic>Depletion</topic><topic>Disease Progression</topic><topic>Drug dosages</topic><topic>End-stage renal disease</topic><topic>Female</topic><topic>Hematuria</topic><topic>Hemodialysis</topic><topic>Histones</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Immunosuppressive agents</topic><topic>Immunotherapy, Adoptive - methods</topic><topic>Kidney diseases</topic><topic>Lupus</topic><topic>Lupus nephritis</topic><topic>Lupus Nephritis - therapy</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Methylprednisolone</topic><topic>Morbidity</topic><topic>Nephritis</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Quality of life</topic><topic>Receptors, Chimeric Antigen</topic><topic>Remission</topic><topic>Remission (Medicine)</topic><topic>Renal 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edition)</jtitle><addtitle>Lancet</addtitle><date>2024-04-27</date><risdate>2024</risdate><volume>403</volume><issue>10437</issue><spage>1627</spage><epage>1630</epage><pages>1627-1630</pages><issn>0140-6736</issn><issn>1474-547X</issn><eissn>1474-547X</eissn><abstract>Morbidity and mortality in juvenile-onset systemic lupus erythematosus are higher than adult-onset disease, and children with lupus nephritis have higher scores on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).2,3 End-stage renal disease and permanent haemodialysis are severe adverse events than can occur due to juvenile-onset and adult-onset systemic lupus erythematosus, with 15% of all patients with lupus nephritis developing end-stage renal disease.4 The therapeutic goal of complete remission of lupus nephritis is only reached in 60% of patients by conventional therapies, including immunosuppressive drugs and B-cell-depleting antibodies,3 and two-thirds of adults with juvenile-onset systemic lupus erythematosus develop organ damage and impaired health-related quality of life without reaching drug-free remission.5 Due to their high B-cell depletion activity, CD19-targeted chimeric antigen receptor (CAR) T cells are a potentially powerful strategy to treat autoimmune diseases, such as systemic lupus erythematosus.6,7 In a small case series of eight patients aged 18–38 years with treatment-refractory systemic lupus erythematosus, adoptive transfer of CD19-targeted CAR T cells induced a deep reset of B cells leading to abrogation of autoreactive antibodies and durable remission, including abrogation of lupus nephritis with a follow-up time of 6–29 months.8 Herein, we report on a 15-year-old female patient with severe and rapidly progressive systemic lupus erythematosus. Low levels of complement and presence of several autoantibodies including anti-nuclear-antibody anti-double-stranded DNA (anti-dsDNA; 4545 IU/mL [normal range is <100 IU/mL]), anti-nucleosome, and anti-histone antibodies were evident. Because renal function further rapidly worsened under therapy escalation with high-dose methylprednisolone and cyclophosphamide, plasma separation was initiated, leading to a reduction in autoantibody levels. At our site (University Hospital Erlangen, Erlangen, Germany), we initiated CD19-targeted CAR T-cell therapy in an expanded access programme for critically ill patients according to the German Arzneimittelgesetz, §21/2 and the Arzneimittel-Härtefall-Verordnung §2 following a mandatory case review by an independent interdisciplinary board. Despite kidney failure, CAR T-cell therapy was safe and well tolerated due to appropriate dose adjustment of lymphodepletion.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>38642568</pmid><doi>10.1016/S0140-6736(24)00424-0</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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ispartof | The Lancet (British edition), 2024-04, Vol.403 (10437), p.1627-1630 |
issn | 0140-6736 1474-547X 1474-547X |
language | eng |
recordid | cdi_proquest_miscellaneous_3043069647 |
source | Elsevier:Jisc Collections:Elsevier Read and Publish Agreement 2022-2024:Freedom Collection (Reading list) |
subjects | Adolescent Adolescents Adoptive transfer Adults Anti-DNA antibodies Antibodies Antihypertensives Arthritis Autoantibodies Autoimmune diseases CD19 antigen Cell therapy Chimeric antigen receptors Chronic conditions Creatinine Cyclophosphamide Cytokine storm Depletion Disease Progression Drug dosages End-stage renal disease Female Hematuria Hemodialysis Histones Humans Hypertension Immunosuppressive agents Immunotherapy, Adoptive - methods Kidney diseases Lupus Lupus nephritis Lupus Nephritis - therapy Lymphocytes Lymphocytes B Lymphocytes T Male Methylprednisolone Morbidity Nephritis Patients Pediatrics Quality of life Receptors, Chimeric Antigen Remission Remission (Medicine) Renal Dialysis Renal failure Renal function Systemic lupus erythematosus Therapy |
title | CAR T-cell therapy rescues adolescent with rapidly progressive lupus nephritis from haemodialysis |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T22%3A05%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CAR%20T-cell%20therapy%20rescues%20adolescent%20with%20rapidly%20progressive%20lupus%20nephritis%20from%20haemodialysis&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Krickau,%20Tobias&rft.date=2024-04-27&rft.volume=403&rft.issue=10437&rft.spage=1627&rft.epage=1630&rft.pages=1627-1630&rft.issn=0140-6736&rft.eissn=1474-547X&rft_id=info:doi/10.1016/S0140-6736(24)00424-0&rft_dat=%3Cproquest_cross%3E3046382071%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3550-d27bb7a52d6553bf379e6361b9e2c3a8b1e68512c5e2af9c58f5acab21d7e7b43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3046382071&rft_id=info:pmid/38642568&rfr_iscdi=true |