BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial
Abstract 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...
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| Language: | English |
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BMC
2025-05-01
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| Series: | Journal of Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s13045-025-01713-2 |
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| author | Hao Yao Shi-hui Ren Lin-hui Wang Ming-qiang Ren Jiao Cai Dan Chen Ying He Si-han Lai Bai-tao Dou Meng-jiao Li Yan-ling Li Ya-li Cen Alex H. Chang Yi Su Ling Qiu Fang-yi Fan |
| author_facet | Hao Yao Shi-hui Ren Lin-hui Wang Ming-qiang Ren Jiao Cai Dan Chen Ying He Si-han Lai Bai-tao Dou Meng-jiao Li Yan-ling Li Ya-li Cen Alex H. Chang Yi Su Ling Qiu Fang-yi Fan |
| author_sort | Hao Yao |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-010cd6a030ef4734870356c83143be76 |
| institution | OA Journals |
| issn | 1756-8722 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-010cd6a030ef4734870356c83143be762025-08-20T02:31:09ZengBMCJournal of Hematology & Oncology1756-87222025-05-011811510.1186/s13045-025-01713-2BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trialHao Yao0Shi-hui Ren1Lin-hui Wang2Ming-qiang Ren3Jiao Cai4Dan Chen5Ying He6Si-han Lai7Bai-tao Dou8Meng-jiao Li9Yan-ling Li10Ya-li Cen11Alex H. Chang12Yi Su13Ling Qiu14Fang-yi Fan15Department of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, The People’s Hospital of Guizhou ProvinceDepartment of Hematology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandEngineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan UniversityDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandDepartment of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater CommandAbstract 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.https://doi.org/10.1186/s13045-025-01713-2BCMAGPRC5DCAR T-cell therapyRelapsed/refractory multiple myelomaExtramedullary diseaseImmunotherapy |
| spellingShingle | Hao Yao Shi-hui Ren Lin-hui Wang Ming-qiang Ren Jiao Cai Dan Chen Ying He Si-han Lai Bai-tao Dou Meng-jiao Li Yan-ling Li Ya-li Cen Alex H. Chang Yi Su Ling Qiu Fang-yi Fan 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 BCMA GPRC5D CAR T-cell therapy Relapsed/refractory multiple myeloma Extramedullary disease Immunotherapy |
| title | BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial |
| title_full | BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial |
| title_fullStr | BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial |
| title_full_unstemmed | BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial |
| title_short | BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial |
| title_sort | bcma gprc5d bispecific car t cell therapy for relapsed refractory multiple myeloma with extramedullary disease a single center single arm phase 1 trial |
| topic | BCMA GPRC5D CAR T-cell therapy Relapsed/refractory multiple myeloma Extramedullary disease Immunotherapy |
| url | https://doi.org/10.1186/s13045-025-01713-2 |
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