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CAR T 细胞治疗复发/难治性 B 细胞急性淋巴细胞白血病患者疗效和安全性的综合分析:系统综述和荟萃分析

英文原题:Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.

PubMed 2024/05/13(内容时间) Ann Med Q1 · IF 4.9(JCR 2025)

研究概要

选择更有效、更安全的 CAR T 细胞治疗对于改善急性白血病的总生存期至关重要。

中文摘要

背景:复发/难治性 B 细胞急性淋巴细胞白血病(r/r B-ALL)是预后困难的儿童癌症。CAR-T 被视为先进治疗,但由于复发率高和不良事件,疗效仍有争议。本研究评估 CAR-T 治疗 r/r B-ALL 的疗效和安全性。 方法:在四个数据库中检索文献。疗效指标包括微小残留病阴性完全缓解(MRD-CR)率和复发率(RR);安全性指标包括细胞因子释放综合征(CRS)及免疫效应细胞相关神经毒性综合征(ICANS)。 结果:与抗 CD19 相比,抗 CD22 的 MRD-CR 事件率最高、RR 最低,疗效更优。CAR-T 联合单倍体干细胞移植可改善 RR。安全性方面,抗 CD19/22 双特异性 CAR-T 的 CRS 率最低,抗 CD22 的 ICANS 最少。共刺激受体分析显示,在抗 CD19 CAR-T 中加入 CD28 可更有效减少复发,且安全性良好。 结论:选择疗效更优且更安全的 CAR-T 治疗对改善急性白血病总生存至关重要。除前景良好的抗 CD22 CAR-T 外,探索共刺激结构域和新的 CD 靶点也可能提高 r/r B-ALL 治疗效果。

展开英文摘要原文

BACKGROUND: Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL. METHODS: The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). RESULTS: Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28 to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles. CONCLUSION: Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.

论文信息

作者
Willyanto SE、Alimsjah YA、Tanjaya K、Tuekprakhon A、Pawestri AR
第一作者单位
Bachelor Study Program of Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.Indonesia
通讯作者单位
Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.Indonesia
文献类型
系统综述 · 荟萃分析 · 非美国政府资助研究
期刊
Annals of medicine2024 Dec
原文标识
PubMed 38738799 · DOI 10.1080/07853890.2024.2349796