决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies.
共纳入 26 项研究,包含 2,246 例患者。
尽管治疗有所进步,多发性骨髓瘤(MM)仍不可治愈,复发或难治性(R/R)病例尤其如此。B细胞成熟抗原(BCMA)是新型免疫疗法的关键靶点,包括CAR-T 细胞疗法和双特异性T细胞衔接器(BiTE);这些疗法在疗效、毒性和可及性方面各不相同。本研究旨在通过系统综述和荟萃分析,比较BCMA靶向CAR-T疗法与BiTE治疗R/R MM的疗效和安全性。我们系统检索PubMed、Embase和Cochrane图书馆截至2024年10月2日的文献,寻找评估BCMA靶向CAR-T或BiTE治疗R/R MM的研究。共纳入26项研究,涉及2,246例患者。采用随机效应荟萃分析和荟萃回归评估汇总疗效及安全性结局,并分析CAR-T构建体和患者特征的影响。CAR-T疗法的总缓解率(ORR)较高,为84%;完全缓解/严格完全缓解(CR/sCR)率为55%。BiTE相应数据分别为65%和41%。双靶点CAR-T疗法(如抗BCMA+抗CD38/CD19)的疗效最高,ORR为92%。CAR-T与较多血液学毒性和细胞因子释放综合征相关;BiTE严重不良事件较少,但感染率较高。荟萃回归证实CAR-T疗效显著优于BiTE。与以往分析不同,本研究整合干预性研究和真实世界数据,评估双靶点CAR-T,并开展具体产品和亚组层面的比较。BCMA靶向CAR-T疗法带来更深度应答,但毒性更高;BiTE安全性更好但效力较弱,有助于制定更个体化的MM BCMA靶向免疫治疗决策。
Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) cases. B-cell maturation antigen (BCMA) is a key target for novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs), which vary in efficacy, toxicity, and accessibility. To compare the efficacy and safety of BCMA-directed CAR-T therapies and BiTEs in R/R MM through a systematic review and meta-analysis. We systematically searched PubMed, Embase, and the Cochrane Library up to October 2, 2024, for studies evaluating BCMA-directed CAR-T or BiTEs therapies in R/R MM. Twenty-six studies comprising 2,246 patients were included. A random-effects meta-analysis and meta-regression were performed to assess pooled efficacy and safety outcomes and examine the impact of CAR-T constructs and patient-level characteristics. CAR-T therapies showed a higher overall response rate (ORR) of 84% and CR/stringent CR (CR/sCR) of 55%, compared to 65% and 41%, respectively, for BiTEs. Dual-targeted CAR-T therapies (e.g., anti-BCMA + anti-CD38/CD19) had the highest efficacy (ORR 92%). CAR-T was associated with more hematologic toxicity and cytokine release syndrome, while BiTEs had fewer severe events but higher infection rates. Meta-regression confirmed CAR-T significantly outperformed BiTEs. Unlike previous analyses, this study integrates interventional and real-world data, evaluates dual-target CAR-Ts, and offers detailed product- and subgroup-level comparisons. BCMA-targeted CAR-T therapies yield deeper responses but greater toxicity. BiTEs offer safer, though less potent, alternatives, supporting more personalized decisions in BCMA-directed immunotherapy for MM.
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