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CAR T 细胞疗法治疗复发或难治性 B 细胞急性淋巴细胞白血病患者的疗效和安全性的综合分析:系统评价和荟萃分析。

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.

机构信息

Bachelor Study Program of Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.

出版信息

Ann Med. 2024 Dec;56(1):2349796. doi: 10.1080/07853890.2024.2349796. Epub 2024 May 13.

Abstract

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 CD28ζ 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.

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)是一种预后极具挑战性的儿科癌症。嵌合抗原受体 T 细胞(CAR T)治疗被认为是一种先进的治疗方法,但由于高复发率和不良反应,其仍存在争议。本研究评估了 CAR T 细胞治疗 r/r B-ALL 的疗效和安全性。

方法

文献检索在四个数据库中进行。疗效参数包括微小残留病灶阴性完全缓解(MRD-CR)和复发率(RR)。安全性参数包括细胞因子释放综合征(CRS)和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 显示出更高的疗效,具有最高的 MRD-CR 发生率和最低的 RR。CAR T 细胞治疗与单倍体造血干细胞移植相结合可改善 RR。在安全性方面,双特异性抗 CD19/22 的 CRS 发生率最低,抗 CD22 的 ICANS 发生率最低。对共刺激受体的分析表明,在抗 CD19 CAR T 细胞中添加 CD28ζ 可降低复发率,同时具有良好的安全性。

结论

选择更有效和更安全的 CAR T 细胞治疗对于改善急性白血病的总生存率至关重要。除了有前景的抗 CD22 CAR T 细胞外,探索共刺激结构域和新的 CD 靶点可能会增强 r/r B-ALL 的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7140/11095278/53ccf8aecd6e/IANN_A_2349796_F0001_C.jpg

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