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However, resistance to CAR-T therapy remains a critical challenge. Investigating the mechanisms underlying CAR-T resistance, including antigen escape, immunosuppression, and CAR-T cell exhaustion, is essential for enhancing the long-term efficacy of this therapeutic approach. This study provides an in-depth review of the latest findings presented at the 66th ASH Annual Meeting.<\/jats:p>","DOI":"10.1186\/s40164-025-00643-6","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T06:51:55Z","timestamp":1742971915000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mechanisms of resistance to CAR-T cell therapy in multiple myeloma: latest updates from the 2024 ASH annual meeting"],"prefix":"10.1186","volume":"14","author":[{"given":"Yuhan","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangxue","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quande","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"issue":"Supplement 1","key":"643_CR1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1182\/blood-2024-201288","volume":"144","author":"F Maura","year":"2024","unstructured":"Maura F, Freeman CL, Lee H, Maclachlan KH, Durante M, Ziccheddu B, et al. Genomic determinants of resistance to Anti-BCMA chimeric antigen receptor T-Cell (CART) therapies in patients with relapsed\/refractory multiple myeloma. Blood. 2024;144(Supplement 1):247.","journal-title":"Blood"},{"issue":"Supplement 1","key":"643_CR2","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood-2024-206347","volume":"144","author":"D Jung","year":"2024","unstructured":"Jung D, Lee H, Chikhale S, Poorebrahim M, Ahn S, Benaoudia S, et al. NF-Kb pathway activation driven by TRAF3 loss mediates resistance to Anti-BCMA T-Cell based therapies in multiple myeloma. Blood. 2024;144(Supplement 1):591.","journal-title":"Blood"},{"issue":"Supplement 1","key":"643_CR3","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1182\/blood-2024-206422","volume":"144","author":"X Chen","year":"2024","unstructured":"Chen X, Huang R, Wang H, Xiao H, Li Q, Zhai Z, et al. Single cell RNA-Seq analysis revealed MIF\/CD74 pathway determinants of BCMA CART resistance in relapsed\/refractory multiple myeloma. Blood. 2024;144(Supplement 1):4764.","journal-title":"Blood"},{"issue":"Supplement 1","key":"643_CR4","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1182\/blood-2024-201194","volume":"144","author":"A Aleman","year":"2024","unstructured":"Aleman A, Zhao R, Grossman L, Sanawar R, Aluri S, Mohindru M, et al. BCMA CART therapy failure in myeloma is associated with immunosuppressive S100A8\/9 overexpression and can be ameliorated with novel monoclonal antibodies. Blood. 2024;144(Supplement 1):589.","journal-title":"Blood"},{"issue":"Supplement 1","key":"643_CR5","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1182\/blood-2024-205226","volume":"144","author":"D Guo","year":"2024","unstructured":"Guo D, Su W, Lu J, Hong L, Li B, Hongming H. Study on the role of Platelet-Activating factor in promoting relapse of multiple myeloma after CAR-T therapy. Blood. 2024;144(Supplement 1):1940.","journal-title":"Blood"},{"issue":"Supplement 1","key":"643_CR6","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1182\/blood-2024-212331","volume":"144","author":"CK Stein","year":"2024","unstructured":"Stein CK, Meermeier EW, Shotts Y, Zhu YX, Shi C-X, Pfeffer K, et al. Abundance of C1q expressing macrophages promotes resistance to modern therapy. Blood. 2024;144(Supplement 1):3275.","journal-title":"Blood"},{"issue":"Supplement 1","key":"643_CR7","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1182\/blood-2024-203007","volume":"144","author":"B Paiva","year":"2024","unstructured":"Paiva B, Manrique I, Thompson EG, Campbell TB, Guerrero C, Martin N, et al. Biological and clinical significance of endogenous and chimeric antigen receptor (CAR) T cell immune profiling in relapsed\/refractory multiple myeloma (RRMM) patients. Blood. 2024;144(Supplement 1):900.","journal-title":"Blood"},{"issue":"Supplement 1","key":"643_CR8","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1182\/blood-2024-205126","volume":"144","author":"Y Xia","year":"2024","unstructured":"Xia Y, Shen X, Shi M, Shen N, Zhu Y, Fan L, et al. Tigit: the potential mechanisms of relapse in multiple myeloma following Anti-BCMA CAR-T therapy and a promising target for improving CAR-T efficacy. Blood. 2024;144(Supplement 1):2033.","journal-title":"Blood"},{"issue":"1","key":"643_CR9","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41467-021-21177-5","volume":"12","author":"MK Samur","year":"2021","unstructured":"Samur MK, Fulciniti M, Aktas Samur A, Bazarbachi AH, Tai YT, Prabhala R, et al. Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma. Nat Commun. 2021;12(1):868.","journal-title":"Nat Commun"},{"issue":"19","key":"643_CR10","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1182\/blood.2019000050","volume":"134","author":"MJ Pont","year":"2019","unstructured":"Pont MJ, Hill T, Cole GO, Abbott JJ, Kelliher J, Salter AI, et al. \u03b3-Secretase Inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134(19):1585\u201397.","journal-title":"Blood"},{"key":"643_CR11","doi-asserted-by":"crossref","first-page":"1433774","DOI":"10.3389\/fimmu.2024.1433774","volume":"15","author":"B Fu","year":"2024","unstructured":"Fu B, Liu R, Gao G, Lin Z, He A. Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy. 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