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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Tác giả: Jiao Cai, Ya-Li Cen, Alex H Chang, Dan Chen, Bai-Tao Dou, Fang-Yi Fan, Ying He, Si-Han Lai, Meng-Jiao Li, Yan-Ling Li, Ling Qiu, Ming-Qiang Ren, Shi-Hui Ren, Yi Su, Lin-Hui Wang, Hao Yao

Ngôn ngữ: eng

Ký hiệu phân loại: 004.125 Specific mainframe computers

Thông tin xuất bản: England : Journal of hematology & oncology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 746775

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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