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.
国家科技期刊平台
NSTL
维普
万方数据
