{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:22:37Z","timestamp":1773832957763,"version":"3.50.1"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biomark Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Light chain amyloidosis (AL) is a rare disease caused by the generalized deposition of misfolded free light chains. Patients with immunoglobulin M gammopathy (IgM) and indolent B-cell lymphoma such as marginal zone lymphoma (MZL) may in some instances develop AL amyloidosis. So far, CAR T cells for AL amyloidosis have only been reported utilizing the B cell maturation antigen as target, while CD19 has so far not been used in AL amyloidosis.<\/jats:p><jats:p>We report the case of a 71-year-old male, diagnosed with systemic AL kappa amyloidosis and MZL, receiving third-generation CAR T cell therapy targeting CD19. Prior treatment included bendamustine\/rituximab and cyclophosphamide\/ dexamethasone with subsequent autologous stem cell transplantation. CAR T application was well tolerated despite heart and kidney amyloid manifestations, and only early low-grade procedure-specific toxicities were observed. A continuous decrease in IgM, kappa light chains and kappa-to-lambda light chain difference was observed in the patient from day\u2009+\u200930 on, resulting in a deep hematological response six months after treatment.<\/jats:p><jats:p>In summary, we present a novel case of CAR T cell treatment with third generation CD19 directed infusion for AL amyloidosis with an underlying secretory active B cell lymphoma, showing that this is an effective treatment modality and can be applied to patients with subsequent AL amyloidosis.<\/jats:p>","DOI":"10.1186\/s40364-023-00532-2","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T11:01:31Z","timestamp":1697281291000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["First third-generation CAR T cell application targeting CD19 for the treatment of systemic IgM AL amyloidosis with underlying marginal zone lymphoma"],"prefix":"10.1186","volume":"11","author":[{"given":"Felix","family":"Korell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Sch\u00f6nland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madelaine","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiavasch","family":"Farid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"M\u00fcller-Tidow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Dreger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Hegenbart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,14]]},"reference":[{"key":"532_CR1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41572-018-0034-3","volume":"4","author":"G Merlini","year":"2018","unstructured":"Merlini G, et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers. 2018;4:38. https:\/\/doi.org\/10.1038\/s41572-018-0034-3.","journal-title":"Nat Rev Dis Primers"},{"key":"532_CR2","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.hoc.2020.08.016","volume":"34","author":"AD Wechalekar","year":"2020","unstructured":"Wechalekar AD, Chakraborty R, Lentzsch S. Systemic Amyloidosis due to Low-Grade Lymphoma. Hematol Oncol Clin North Am. 2020;34:1027\u201339. https:\/\/doi.org\/10.1016\/j.hoc.2020.08.016.","journal-title":"Hematol Oncol Clin North Am"},{"key":"532_CR3","doi-asserted-by":"publisher","first-page":"5156","DOI":"10.1158\/1078-0432.CCR-22-0637","volume":"28","author":"S Kfir-Erenfeld","year":"2022","unstructured":"Kfir-Erenfeld S, et al. Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis. Clin Cancer Res. 2022;28:5156\u201366. https:\/\/doi.org\/10.1158\/1078-0432.CCR-22-0637.","journal-title":"Clin Cancer Res"},{"key":"532_CR4","doi-asserted-by":"publisher","unstructured":"Oliver-Caldes A, et al. First report of CART treatment in AL amyloidosis and relapsed\/refractory multiple myeloma. J Immunother Cancer. 2021;9. https:\/\/doi.org\/10.1136\/jitc-2021-003783.","DOI":"10.1136\/jitc-2021-003783"},{"key":"532_CR5","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1182\/blood-2014-04-570010","volume":"124","author":"G Palladini","year":"2014","unstructured":"Palladini G, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124:2325\u201332. https:\/\/doi.org\/10.1182\/blood-2014-04-570010.","journal-title":"Blood"},{"key":"532_CR6","doi-asserted-by":"publisher","first-page":"3420","DOI":"10.1182\/blood-2012-12-473066","volume":"121","author":"AD Wechalekar","year":"2013","unstructured":"Wechalekar AD, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013;121:3420\u20137. https:\/\/doi.org\/10.1182\/blood-2012-12-473066.","journal-title":"Blood"},{"key":"532_CR7","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13045-023-01470-0","volume":"16","author":"ML Schubert","year":"2023","unstructured":"Schubert ML, et al. Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. J Hematol Oncol. 2023;16:79. https:\/\/doi.org\/10.1186\/s13045-023-01470-0.","journal-title":"J Hematol Oncol"},{"key":"532_CR8","doi-asserted-by":"publisher","first-page":"4541","DOI":"10.1200\/JCO.2011.37.7614","volume":"30","author":"G Palladini","year":"2012","unstructured":"Palladini G, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30:4541\u20139. https:\/\/doi.org\/10.1200\/JCO.2011.37.7614.","journal-title":"J Clin Oncol"},{"key":"532_CR9","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1038\/s41409-022-01756-w","volume":"57","author":"K Wudhikarn","year":"2022","unstructured":"Wudhikarn K, Perales MA. Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy. Bone Marrow Transplant. 2022;57:1477\u201388. https:\/\/doi.org\/10.1038\/s41409-022-01756-w.","journal-title":"Bone Marrow Transplant"}],"container-title":["Biomarker Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-023-00532-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40364-023-00532-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-023-00532-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T10:52:55Z","timestamp":1700477575000},"score":1,"resource":{"primary":{"URL":"https:\/\/biomarkerres.biomedcentral.com\/articles\/10.1186\/s40364-023-00532-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,14]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["532"],"URL":"https:\/\/doi.org\/10.1186\/s40364-023-00532-2","relation":{},"ISSN":["2050-7771"],"issn-type":[{"value":"2050-7771","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,14]]},"assertion":[{"value":"23 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval and approvals from the local and federal competent authorities were granted (Ethics Committee of the Medical Faculty, University Heidelberg; October 2017, AFmu-405\/2017) and the patient underwent treatment in analogy with the HD-CAR-1 trial construct as a compassionate use. According to the Declaration of Helsinki, written informed consent from the patient was obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable. Data presented in this study has been de-identified and contains no images, videos or individual identifiers.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"91"}}