CAR-T细胞疗法在儿童及年轻成人B细胞急性淋巴细胞白血病中不断演变的格局
The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia
自2017年替沙仑赛获批以来，嵌合抗原受体（CAR）T细胞疗法已使多名复发难治患者获得深度且往往持久的缓解，真实世界数据亦显示其在婴儿、唐氏综合征及髓外白血病等复杂人群中的获益。然而近半数患者仍会复发。贝林妥欧单抗（一种双特异性T细胞衔接器）纳入治疗方案后，从根本上改变了治疗格局，促使人们重新评估CAR-T的最佳应用时机。本文综述CAR-T在儿童、青少年和年轻成人B细胞急性淋巴细胞白血病中的当前用法，并讨论其预期变化及输注后管理，指出需要新型构造、更好的毒性缓解和疾病监测。
为什么推荐给您：常规综述，梳理已获批CAR-T疗法的应用，无新数据或新技术。
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摘要Abstract
Chimeric antigen receptor (CAR) T cells have demonstrated remarkable ability to render multiple relapsed and refractory patients into a deep and often durable remission. Since initial FDA approval of tisagenlecleucel in 2017, real-world data have shown the benefit of this therapy, even among historically complex populations, such as infants, children with Down syndrome, and those with extramedullary leukemia. Despite the success of CAR T cell therapy, nearly half of patients tend to show relapsed disease, demanding ongoing advancements. Furthermore, the incorporation of the bispecific T cell engager, blinatumomab, into B cell acute lymphoblastic leukemia (B-ALL) therapy has fundamentally shifted the treatment paradigm, calling for a reevaluation of the optimal application of CAR T cells. In this review, we describe the current usage of CAR T cells in children, adolescents, and young adults (CAYAs) with B-ALL and discuss anticipated changes to CAR T cell therapy and post-infusion management. Upfront use of blinatumomab will require novel approaches to relapsed disease, including the use of CAR T cells earlier in therapy. Limited durability of the currently approved CAR T cells will require novel constructs along with improved toxicity mitigation and refinements in post-CAR disease surveillance and therapy. While CAR T cells have made an incredible impact on the field, there is much work due to improve outcomes for CAYAs with B-ALL.