BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial
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.
基金:
This work was supported by Sichuan
Science and Technology Program (2024 NSFSC1292 and 2021YJ0145); the
incubation program of General Hospital of Western Theater command
(2021-XZYG-C45 and 2021-XZYG-C46) and the general program of General
Hospital of Western Theater Command (2021-XZYG-B32).
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
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Yao Hao,Ren Shi-hui,Wang Lin-hui,et al.BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial[J].JOURNAL OF HEMATOLOGY & ONCOLOGY.2025,18(1):doi:10.1186/s13045-025-01713-2.
APA:
Yao, Hao,Ren, Shi-hui,Wang, Lin-hui,Ren, Ming-qiang,Cai, Jiao...&Fan, Fang-yi.(2025).BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial.JOURNAL OF HEMATOLOGY & ONCOLOGY,18,(1)
MLA:
Yao, Hao,et al."BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial".JOURNAL OF HEMATOLOGY & ONCOLOGY 18..1(2025)