Zhongguo quanke yixue (Mar 2024)
Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma: a Meta-analysis
Abstract
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.
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