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.
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引用次数: 0
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.
背景：复发/难治性 B 细胞急性淋巴细胞白血病（r/r B-ALL）是预后极具挑战性的儿科癌症。CAR T细胞治疗被认为是一种先进的治疗方法，但由于复发率高和不良反应多，仍存在争议。本研究评估了CAR T细胞疗法治疗r/r B-ALL的有效性和安全性：方法：在四个数据库中进行文献检索。疗效参数包括最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显示出更优越的疗效，MRD-CR事件发生率最高，RR最低。将CAR T细胞疗法与单倍体干细胞移植相结合可提高RR。安全性方面，双特异性抗CD19/22的CRS率最低，抗CD22的ICANS最少。对成本刺激受体的分析表明，在抗CD19 CAR T细胞中加入CD28ζ可在减少复发方面显示出更优越的疗效，同时具有良好的安全性：结论：选择一种更有效、更安全的 CAR T 细胞疗法对于提高急性白血病患者的总生存率至关重要。结论：选择更有效、更安全的 CAR T 细胞疗法对提高急性白血病患者的总体生存率至关重要。除了前景广阔的抗 CD22 CAR T 细胞外，探索 costimulatory domains 和新的 CD 靶点也能提高 r/r B-ALL 的治疗效果。
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