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The management of potential relapses is currently unclear. Here we report on a 45-year-old woman with treatment-refractory Jo-1-associated anti-synthetase syndrome, who initially achieved disease remission after CD19 CAR T cell therapy but then experienced disease relapse after 9 months. After reinfusion of the same product, CAR T cells failed to expand and T cells targeting the CD19 CAR were detected. Despite full-dose lymphodepletion, no clinical response was observed. After bridging with anti-CD38 antibody daratumumab, which was efficacious with limited durability, plasma-cell-targeting B-cell maturation antigen (BCMA) CAR T cell therapy was performed. BCMA CAR T cells expanded, cleared plasma cells in lymphoid tissue, reduced autoantibody levels and re-induced stable drug-free remission. This case highlights the challenges in CAR T cell reinfusion, the potential of alternative targets and products, and suggests that the depletion of plasma cells may enhance therapeutic outcomes in patients who become treatment-refractory.<\/jats:p>","DOI":"10.1038\/s41591-025-03718-3","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T12:12:52Z","timestamp":1744891972000},"page":"1793-1797","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["BCMA CAR T cells in a patient with relapsing idiopathic inflammatory myositis after initial and repeat therapy with CD19 CAR T cells"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-5839","authenticated-orcid":false,"given":"Fabian","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wirsching","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"V\u00f6lkl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Tur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-6711","authenticated-orcid":false,"given":"Maria Gabriella","family":"Raimondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jule","family":"Taubmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8168-7542","authenticated-orcid":false,"given":"Sascha","family":"Kretschmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Aigner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-3349","authenticated-orcid":false,"given":"Markus","family":"Eckstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sp\u00f6rl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Kharboutli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-8707","authenticated-orcid":false,"given":"Sebastian","family":"B\u00f6ltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Atzinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Munoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-9615","authenticated-orcid":false,"given":"Georg","family":"Schett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0685-4483","authenticated-orcid":false,"given":"Andreas","family":"Mackensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2873-5135","authenticated-orcid":false,"given":"Ricardo","family":"Grieshaber-Bouyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"3718_CR1","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa2308917","volume":"390","author":"F Muller","year":"2024","unstructured":"Muller, F. et al. CD19 CAR T-cell therapy in autoimmune disease \u2013 a case series with follow-up. N. Engl. J. Med. 390, 687\u2013700 (2024).","journal-title":"N. Engl. J. Med."},{"key":"3718_CR2","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1038\/s41591-022-02017-5","volume":"28","author":"A Mackensen","year":"2022","unstructured":"Mackensen, A. et al. Anti-CD19 CAR T-cell therapy for refractory systemic lupus erythematosus. Nat. Med. 28, 2124\u20132132 (2022).","journal-title":"Nat. Med."},{"key":"3718_CR3","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1016\/S0140-6736(23)01126-1","volume":"402","author":"G Schett","year":"2023","unstructured":"Schett, G., Mackensen, A. & Mougiakakos, D. CAR T-cell therapy in autoimmune diseases. Lancet 402, 2034\u20132044 (2023).","journal-title":"Lancet"},{"key":"3718_CR4","doi-asserted-by":"crossref","unstructured":"Taubmann, J. et al. Rescue therapy of antisynthetase syndrome with CD19-targeted CAR-T cells after failure of several B-cell depleting antibodies. Rheumatol. 63, e12\u2013e14 (2024).","DOI":"10.1093\/rheumatology\/kead330"},{"key":"3718_CR5","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1172\/JCI85309","volume":"126","author":"CJ Turtle","year":"2016","unstructured":"Turtle, C. J. et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J. Clin. Invest. 126, 2123\u20132138 (2016).","journal-title":"J. Clin. Invest."},{"key":"3718_CR6","doi-asserted-by":"publisher","first-page":"e003604","DOI":"10.1136\/rmdopen-2023-003604","volume":"9","author":"MT Holzer","year":"2023","unstructured":"Holzer, M. T. et al. Daratumumab for autoimmune diseases: a systematic review. 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Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 113, 214\u2013223 (2009).","journal-title":"Blood"},{"key":"3718_CR13","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1056\/NEJMc2107725","volume":"385","author":"D Mougiakakos","year":"2021","unstructured":"Mougiakakos, D. et al. CD19-targeted CAR T cells in refractory systemic lupus erythematosus. N. Engl. J. Med. 385, 567\u2013569 (2021).","journal-title":"N. Engl. J. Med."},{"key":"3718_CR14","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/art.42784","volume":"76","author":"J Taubmann","year":"2024","unstructured":"Taubmann, J. et al. CD19 chimeric antigen receptor T cell treatment: unraveling the role of B cells in systemic lupus erythematosus. 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G.S. has received speaker honoraria from BMS, Cabaletta, Kyverna, Janssen, Miltenyi and Novartis. A.M. has received research funding from Kyverna and Miltenyi Biomedicine along with consulting fees from Biontech, BMS\/Celgene, Century Therapeutics, KITE\/Gilead, Miltenyi Biomedicine and Novartis. R.G.-B. has received research support from Kyverna and speaker honoraria from BMS, Kyverna and Novartis. No commercial sponsor was involved in the study design, interpretation or writing of the manuscript. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}