Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma
BackgroundClinical studies have demonstrated the high efficacy of using chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) and orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) to treat relapsed or refractory multiple myeloma (RRMM). In this study,...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1466443/full |
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| author | Xu Yang Feiqing Wang Feiqing Wang Xiaoshuang Yuan Bo Yang Juan Chen Jinyang Cheng Guangyang Liu Dongxin Tang Xiao Xu Sanbin Wang Zhixu He Yang Liu Yanju Li |
| author_facet | Xu Yang Feiqing Wang Feiqing Wang Xiaoshuang Yuan Bo Yang Juan Chen Jinyang Cheng Guangyang Liu Dongxin Tang Xiao Xu Sanbin Wang Zhixu He Yang Liu Yanju Li |
| author_sort | Xu Yang |
| collection | DOAJ |
| description | BackgroundClinical studies have demonstrated the high efficacy of using chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) and orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) to treat relapsed or refractory multiple myeloma (RRMM). In this study, we compared the efficacy and safety of BCMA CAR-T-cell therapy (BCMA CAR-T) and GPRC5D CAR T-cell therapy (GPRC5D CAR-T) in patients with RRMM.MethodsWe retrieved and included eligible clinical trials of BCMA or GPRC5D CAR-T for RRMM patients. The primary outcomes for efficacy were overall response rate (ORR), complete response rate (CRR), minimal residual disease (MRD) negativity, and relapse rate. The primary outcomes for safety were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).ResultsWe incorporated 18 early-phase, single-arm clinical trials, which included 503 and 133 patients receiving BCMA CAR-T and GPRC5D CAR-T, respectively. For the GPRC5D CAR-T cohort, the estimated ORR, CRR, MRD negativity rate, and relapse rate were found to be 89.8% [95% confidence interval (CI), 82.8%–96.9%], 50.5% (95% CI, 38.0%–62.9%), 78.8% (95% CI, 53.0%–100%), and 26.0% (95% CI, 7.4%–44.6%), respectively. In the BCMA CAR-T group, the ORR was 76.3% (95% CI, 67.9%–84.7%), the CRR was 34.3% (95% CI, 25.9%–42.7%), the MRD negativity rate was 76.5% (95% CI, 63.1%–90.0%), and the recurrence rate was 57.3% (95% CI, 47.7%–66.9%). These values were significantly lower than those observed in the GPRC5D CAR-T cohort. Both BCMA and GPRC5D CAR-T demonstrated acceptable safety. The estimated incidence of BCMA CAR-T resulting in grade 3–5 CRS and ICANS was only 5.4% (95% CI, 2.0%–10.4%) and 3.3% (95% CI, 0.6%–8.0%), respectively. The estimated incidence of GPRC5D CAR-T resulting in grade 3–5 CRS and ICANS was only 1.6% (95% CI, 0.0%–6.5%) and 2.7% (95% CI, 0.7%–6.2%), respectively.ConclusionGPRC5D CAR-T potentially demonstrates enhanced effectiveness relative to BCMA CAR-T in treating patients with RRMM. Therefore, GPRC5D CAR-T can be regarded as the preferred therapeutic option for RRMM, particularly among patients who have undergone relapse subsequent to BCMA CAR-T treatment. |
| format | Article |
| id | doaj-art-72a35c088a064811a223fe3dafaa1c50 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-72a35c088a064811a223fe3dafaa1c502024-12-23T09:12:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14664431466443Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myelomaXu Yang0Feiqing Wang1Feiqing Wang2Xiaoshuang Yuan3Bo Yang4Juan Chen5Jinyang Cheng6Guangyang Liu7Dongxin Tang8Xiao Xu9Sanbin Wang10Zhixu He11Yang Liu12Yanju Li13Clinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaClinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, ChinaDepartment of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaClinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaClinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaClinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaClinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaClinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaFourth Medical Center, People’s Liberation Army General Hospital, Beijing, ChinaDepartment of Hematology, The 920th Hospital of Joint Logistics Support Force, Kunming, Yunnan, ChinaKey Laboratory of Adult Stem Cell Translational Research, Chinese Academy of Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, ChinaClinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaDepartment of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaBackgroundClinical studies have demonstrated the high efficacy of using chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) and orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) to treat relapsed or refractory multiple myeloma (RRMM). In this study, we compared the efficacy and safety of BCMA CAR-T-cell therapy (BCMA CAR-T) and GPRC5D CAR T-cell therapy (GPRC5D CAR-T) in patients with RRMM.MethodsWe retrieved and included eligible clinical trials of BCMA or GPRC5D CAR-T for RRMM patients. The primary outcomes for efficacy were overall response rate (ORR), complete response rate (CRR), minimal residual disease (MRD) negativity, and relapse rate. The primary outcomes for safety were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).ResultsWe incorporated 18 early-phase, single-arm clinical trials, which included 503 and 133 patients receiving BCMA CAR-T and GPRC5D CAR-T, respectively. For the GPRC5D CAR-T cohort, the estimated ORR, CRR, MRD negativity rate, and relapse rate were found to be 89.8% [95% confidence interval (CI), 82.8%–96.9%], 50.5% (95% CI, 38.0%–62.9%), 78.8% (95% CI, 53.0%–100%), and 26.0% (95% CI, 7.4%–44.6%), respectively. In the BCMA CAR-T group, the ORR was 76.3% (95% CI, 67.9%–84.7%), the CRR was 34.3% (95% CI, 25.9%–42.7%), the MRD negativity rate was 76.5% (95% CI, 63.1%–90.0%), and the recurrence rate was 57.3% (95% CI, 47.7%–66.9%). These values were significantly lower than those observed in the GPRC5D CAR-T cohort. Both BCMA and GPRC5D CAR-T demonstrated acceptable safety. The estimated incidence of BCMA CAR-T resulting in grade 3–5 CRS and ICANS was only 5.4% (95% CI, 2.0%–10.4%) and 3.3% (95% CI, 0.6%–8.0%), respectively. The estimated incidence of GPRC5D CAR-T resulting in grade 3–5 CRS and ICANS was only 1.6% (95% CI, 0.0%–6.5%) and 2.7% (95% CI, 0.7%–6.2%), respectively.ConclusionGPRC5D CAR-T potentially demonstrates enhanced effectiveness relative to BCMA CAR-T in treating patients with RRMM. Therefore, GPRC5D CAR-T can be regarded as the preferred therapeutic option for RRMM, particularly among patients who have undergone relapse subsequent to BCMA CAR-T treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1466443/fullB-cell maturation antigenG protein-coupled receptorclass C group 5 member Dcar-Trelapsed or refractory multiple myeloma |
| spellingShingle | Xu Yang Feiqing Wang Feiqing Wang Xiaoshuang Yuan Bo Yang Juan Chen Jinyang Cheng Guangyang Liu Dongxin Tang Xiao Xu Sanbin Wang Zhixu He Yang Liu Yanju Li Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma Frontiers in Immunology B-cell maturation antigen G protein-coupled receptor class C group 5 member D car-T relapsed or refractory multiple myeloma |
| title | Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma |
| title_full | Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma |
| title_fullStr | Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma |
| title_full_unstemmed | Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma |
| title_short | Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma |
| title_sort | efficacy and safety of chimeric antigen receptor t cells targeting bcma and gprc5d in relapsed or refractory multiple myeloma |
| topic | B-cell maturation antigen G protein-coupled receptor class C group 5 member D car-T relapsed or refractory multiple myeloma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1466443/full |
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