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BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial

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机构: [1]Chinese Peoples Liberat Army G, Gen Hosp Western Theater Command, Dept Hematol, Chengdu 610083, Sichuan, Peoples R China [2]Natl Clin Res Ctr Hematol Dis, Branch, Chengdu 610083, Sichuan, Peoples R China [3]Sichuan Clin Res Ctr Hematol Dis, Chengdu 610083, Peoples R China [4]North Sichuan Med Coll, Dept Clin Med, Nanchong 637000, Sichuan, Peoples R China [5]North Sichuan Med Coll, Inst Basic Med, Nanchong 637000, Sichuan, Peoples R China [6]Peoples Hosp Guizhou Prov, Dept Hematol, Guiyang 550002, Guizhou, Peoples R China [7]Zunyi Med Univ, Affiliated Hosp, Dept Hematol, Zunyi 563000, Guizhou, Peoples R China [8]Fudan Univ, Inst Genet, Engn Res Ctr Gene Technol, Sch Life Sci, Shanghai 200438, Peoples R China [9]Shanghai YaKe Biotechnol Ltd, Yangpu Dist, Shanghai 200090, Peoples R China
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关键词: BCMA GPRC5D CAR T-cell therapy Relapsed/refractory multiple myeloma Extramedullary disease Immunotherapy

摘要:
Relapsed/refractory multiple myeloma (RRMM) with extramedullary disease (EMD) represents a challenging condition, with limited treatment options and poor prognosis. We conducted a phase 1 clinical trial to evaluate the safety and effectiveness of a novel bispecific chimeric antigen receptor (CAR) T-cell therapy targeting two antigens, B-cell maturation antigen and G protein-coupled receptor class C group 5 member D (BCMA/GPRC5D), in this high-risk population. A total of 12 patients were enrolled, of whom 3 were excluded due to disease progression or death before CAR T-cell infusion, despite meeting the inclusion criteria, leaving 9 for analysis. The median follow-up was 6.08 months (Interquartile Range [IQR]: 0.9-16.5). All patients received BCMA/GPRC5D bispecific CAR T-cell therapy after bridging therapy with localized radiotherapy or Elranatamab. Efficacy assessments revealed that 100% of patients achieved partial response (PR) or better, with 44.4% achieving complete response (CR). Common adverse events included hematological toxicities such as anemia, leukopenia, and thrombocytopenia. Cytokine release syndrome (CRS) occurred in 66.7% of patients, all of which were grade 1-2, and no neurotoxicity (ICANS) was observed. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 60% and 63%, respectively. Median OS and PFS were not reached. Collectively, these findings highlight a potential therapeutic strategy involving BCMA/GPRC5D dual-targeted CAR T-cell therapy for patients with aggressive forms of multiple myeloma, particularly those with extramedullary disease, and support the need for further exploration and validation in larger, multi-center clinical studies.

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大类 | 1 区 医学
小类 | 1 区 血液学 1 区 肿瘤学
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大类 | 1 区 医学
小类 | 1 区 血液学 1 区 肿瘤学
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Q1 HEMATOLOGY Q1 ONCOLOGY
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Q1 HEMATOLOGY Q1 ONCOLOGY

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第一作者机构: [1]Chinese Peoples Liberat Army G, Gen Hosp Western Theater Command, Dept Hematol, Chengdu 610083, Sichuan, Peoples R China [2]Natl Clin Res Ctr Hematol Dis, Branch, Chengdu 610083, Sichuan, Peoples R China [3]Sichuan Clin Res Ctr Hematol Dis, Chengdu 610083, Peoples R China [5]North Sichuan Med Coll, Inst Basic Med, Nanchong 637000, Sichuan, Peoples R China
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通讯机构: [1]Chinese Peoples Liberat Army G, Gen Hosp Western Theater Command, Dept Hematol, Chengdu 610083, Sichuan, Peoples R China [2]Natl Clin Res Ctr Hematol Dis, Branch, Chengdu 610083, Sichuan, Peoples R China [3]Sichuan Clin Res Ctr Hematol Dis, Chengdu 610083, Peoples R China [4]North Sichuan Med Coll, Dept Clin Med, Nanchong 637000, Sichuan, Peoples R China [5]North Sichuan Med Coll, Inst Basic Med, Nanchong 637000, Sichuan, Peoples R China
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