Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis
Background Chimeric antigen receptor (CAR) -T cell immunotherapy has achieved good therapeutic effect in multiple myeloma (MM) , and the most common target is B cell maturation antigen (BCMA) . The disadvantage of single target CAR-T cell immunotherapy is that it can lead to disease resistance and r...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | zho |
| Published: |
Chinese General Practice Publishing House Co., Ltd
2024-03-01
|
| Series: | Zhongguo quanke yixue |
| Subjects: | |
| Online Access: | https://www.chinagp.net/fileup/1007-9572/PDF/20230454.pdf |
| _version_ | 1797216569233768448 |
|---|---|
| author | YU Haibo, ZHANG Tianyu, LI Xin, ZHANG Jiajia, SHEN Man, ZHAN Xiaokai, TANG Ran, FAN Sibin, ZHAO Fengyi, HUANG Zhongxia |
| author_facet | YU Haibo, ZHANG Tianyu, LI Xin, ZHANG Jiajia, SHEN Man, ZHAN Xiaokai, TANG Ran, FAN Sibin, ZHAO Fengyi, HUANG Zhongxia |
| author_sort | YU Haibo, ZHANG Tianyu, LI Xin, ZHANG Jiajia, SHEN Man, ZHAN Xiaokai, TANG Ran, FAN Sibin, ZHAO Fengyi, HUANG Zhongxia |
| collection | DOAJ |
| description | Background Chimeric antigen receptor (CAR) -T cell immunotherapy has achieved good therapeutic effect in multiple myeloma (MM) , and the most common target is B cell maturation antigen (BCMA) . The disadvantage of single target CAR-T cell immunotherapy is that it can lead to disease resistance and recurrence, which may be related to antigen escape. Therefore, the dual-targeted CAR-T cell therapy for refractory-relapsed multiple myeloma (RRMM) has been improved and developed, but there is still a lack of systematic clinical analysis in this field. Objective A meta-analysis was conducted on the efficacy and safety of dual-targeted CAR-T cell therapy for RRMM patients. Methods PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, and VIP were searched for single-group rate studies on dual-targeted CAR-T cell therapy in patients with RRMM from inception to 2023-02-06. The data were extracted for collection by 2 investigators using a self-designed form and the quality of literature was evaluated using the methodological index for non-randomized studies (MINORS) . The data analysis was conducted using RStudio software. Results A total of 9 clinical studies, involving 200 RRMM patients who had previously received multi-line therapy were included in the study. Dual-targeted CAR-T cell therapy can be mainly divided into four categories based on different targets of BCMA/CD19, BCMA/CD38, BCMA/TACI, and BCMA/CS1, of which the BCMA+CD19 target is more studied. Dual-targeted CAR-T cell therapy also can be divided into four categories of bispecific categories, combined/sequential infusion of two different CAR-T cells, bicistronic or cotransduction according to the different forms of infusion. Meta-analysis showed that the overall response rate (ORR) of dual-targeted CAR-T cells for RRMM was 90.0% (95%CI=0.849-0.943) , and the complete response rate (CRR) was 54.6% (95%CI=0.416-0.673) , the negative rate of minimal residual disease (MRD) was 75.6% (95%CI=0.489-0.952) , the ORR of extramedullary diseases (EMD) was 55.1% (95%CI=0.234-0.851) , the recurrence rate at the last follow-up was 29.7% (95%CI=0.141-0.454) , and the survival rate was 75.6% (95%CI=0.554-0.915) . The incidence of grade 3 to 4 cytokine release syndrome (CRS) was 16.4% (95%CI=0.094-0.245) , and the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 4.0% (95%CI=0-0.120) . Sensitivity analysis suggested stable results. The results of Egger's test indicated a potential bias risk for ORR (P=0.03) and overall response rate of EMD (P=0.02) . Meanwhile, no publication bias was suggested for CRR (P=0.53) , MRD negative rate (P=0.79) , recurrence rate at the last follow-up (P=0.71) , survival rate (P=0.98) , incidence of grade 3-4 CRS (P=0.90) , and incidence of ICANS (P=0.30) . Conclusion Dual-targeted CAR-T cell therapy for RRMM has shown favorable efficacy and safety, and multicenter, large-sample, and longer follow-up studies are needed to further evaluate its efficacy and safety. |
| first_indexed | 2024-04-24T11:48:03Z |
| format | Article |
| id | doaj.art-6fa5885c5f6e4628aa9263abe7165eaa |
| institution | Directory Open Access Journal |
| issn | 1007-9572 |
| language | zho |
| last_indexed | 2024-04-24T11:48:03Z |
| publishDate | 2024-03-01 |
| publisher | Chinese General Practice Publishing House Co., Ltd |
| record_format | Article |
| series | Zhongguo quanke yixue |
| spelling | doaj.art-6fa5885c5f6e4628aa9263abe7165eaa2024-04-09T09:11:15ZzhoChinese General Practice Publishing House Co., LtdZhongguo quanke yixue1007-95722024-03-01270898599410.12114/j.issn.1007-9572.2023.0454Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysisYU Haibo, ZHANG Tianyu, LI Xin, ZHANG Jiajia, SHEN Man, ZHAN Xiaokai, TANG Ran, FAN Sibin, ZHAO Fengyi, HUANG Zhongxia0Department of Hematology and Oncology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, ChinaBackground Chimeric antigen receptor (CAR) -T cell immunotherapy has achieved good therapeutic effect in multiple myeloma (MM) , and the most common target is B cell maturation antigen (BCMA) . The disadvantage of single target CAR-T cell immunotherapy is that it can lead to disease resistance and recurrence, which may be related to antigen escape. Therefore, the dual-targeted CAR-T cell therapy for refractory-relapsed multiple myeloma (RRMM) has been improved and developed, but there is still a lack of systematic clinical analysis in this field. Objective A meta-analysis was conducted on the efficacy and safety of dual-targeted CAR-T cell therapy for RRMM patients. Methods PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, and VIP were searched for single-group rate studies on dual-targeted CAR-T cell therapy in patients with RRMM from inception to 2023-02-06. The data were extracted for collection by 2 investigators using a self-designed form and the quality of literature was evaluated using the methodological index for non-randomized studies (MINORS) . The data analysis was conducted using RStudio software. Results A total of 9 clinical studies, involving 200 RRMM patients who had previously received multi-line therapy were included in the study. Dual-targeted CAR-T cell therapy can be mainly divided into four categories based on different targets of BCMA/CD19, BCMA/CD38, BCMA/TACI, and BCMA/CS1, of which the BCMA+CD19 target is more studied. Dual-targeted CAR-T cell therapy also can be divided into four categories of bispecific categories, combined/sequential infusion of two different CAR-T cells, bicistronic or cotransduction according to the different forms of infusion. Meta-analysis showed that the overall response rate (ORR) of dual-targeted CAR-T cells for RRMM was 90.0% (95%CI=0.849-0.943) , and the complete response rate (CRR) was 54.6% (95%CI=0.416-0.673) , the negative rate of minimal residual disease (MRD) was 75.6% (95%CI=0.489-0.952) , the ORR of extramedullary diseases (EMD) was 55.1% (95%CI=0.234-0.851) , the recurrence rate at the last follow-up was 29.7% (95%CI=0.141-0.454) , and the survival rate was 75.6% (95%CI=0.554-0.915) . The incidence of grade 3 to 4 cytokine release syndrome (CRS) was 16.4% (95%CI=0.094-0.245) , and the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 4.0% (95%CI=0-0.120) . Sensitivity analysis suggested stable results. The results of Egger's test indicated a potential bias risk for ORR (P=0.03) and overall response rate of EMD (P=0.02) . Meanwhile, no publication bias was suggested for CRR (P=0.53) , MRD negative rate (P=0.79) , recurrence rate at the last follow-up (P=0.71) , survival rate (P=0.98) , incidence of grade 3-4 CRS (P=0.90) , and incidence of ICANS (P=0.30) . Conclusion Dual-targeted CAR-T cell therapy for RRMM has shown favorable efficacy and safety, and multicenter, large-sample, and longer follow-up studies are needed to further evaluate its efficacy and safety.https://www.chinagp.net/fileup/1007-9572/PDF/20230454.pdfmultiple myeloma|refractory-relapsed multiple myelomachimeric|antigen receptor t-cell immunotherapy|meta-analysis |
| spellingShingle | YU Haibo, ZHANG Tianyu, LI Xin, ZHANG Jiajia, SHEN Man, ZHAN Xiaokai, TANG Ran, FAN Sibin, ZHAO Fengyi, HUANG Zhongxia Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis Zhongguo quanke yixue multiple myeloma|refractory-relapsed multiple myelomachimeric|antigen receptor t-cell immunotherapy|meta-analysis |
| title | Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis |
| title_full | Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis |
| title_fullStr | Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis |
| title_full_unstemmed | Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis |
| title_short | Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis |
| title_sort | efficacy and safety of dual targeted chimeric antigen receptor t cell therapy in patients with refractory relapsed multiple myeloma a meta analysis |
| topic | multiple myeloma|refractory-relapsed multiple myelomachimeric|antigen receptor t-cell immunotherapy|meta-analysis |
| url | https://www.chinagp.net/fileup/1007-9572/PDF/20230454.pdf |
| work_keys_str_mv | AT yuhaibozhangtianyulixinzhangjiajiashenmanzhanxiaokaitangranfansibinzhaofengyihuangzhongxia efficacyandsafetyofdualtargetedchimericantigenreceptortcelltherapyinpatientswithrefractoryrelapsedmultiplemyelomaametaanalysis |