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CD19 靶向 CAR-T 细胞疗法在复发/难治性侵袭性 B 细胞淋巴瘤患者中的疗效与安全性:来自 JULIET、ZUMA-1 和 TRANSCEND 试验的观察结果

英文原题:Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials.

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Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials.

PubMed 2021/08/13(内容时间) Am J Hematol Q1 · IF 9.4(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

靶向CD19的嵌合抗原受体(CAR)T细胞疗法改善了许多复发/难治性侵袭性B细胞淋巴瘤患者的结局。2017年,阿基仑赛和随后获批的替沙仑赛,成为首批获准用于既往接受两线治疗后复发或难治的高级别B细胞淋巴瘤或弥漫性大B细胞淋巴瘤(DLBCL)患者的CAR-T 产品;利基迈仑赛于2021年获批。各类CAR-T 疗法关键性试验的安全性和疗效结果均已有报道。尽管这些疗法针对大B细胞淋巴瘤患者共同的未满足需求,且采用相似的CAR技术,但不同产品在制备工艺、关键性试验设计和数据报告方面存在差异。阿基仑赛和替沙仑赛上市后的早期应用报告,首次提供了在真实世界中验证患者特征对CAR-T 疗效和安全性影响的机会。今后,CAR-T 治疗后的患者管理需要制定相应策略,以监测缓解是否持续以及可能出现的长期副作用。本综述介绍了主要产品特征、临床试验方案设计及关键试验结局,并讨论近期真实世界中接受阿基仑赛或替沙仑赛患者的特征、疗效和安全性数据。

最后,综述CAR-T 输注后的管理,并展望即将开展的CAR-T 临床试验。

展开英文摘要原文

Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell products for patients with high-grade B-cell lymphomas or diffuse large B-cell lymphoma (DLBCL) who are relapsed or refractory to 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR-T cell therapy have been reported.

Despite addressing a common unmet need in the large B-cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR-T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world.

Going forward, caring for patients after CAR-T cell therapy will require strategies to monitor patients for sustained responses and potential long-term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented.

We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world.

Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR-T cell therapies.

论文信息

作者
Westin JR、Kersten MJ、Salles G、Abramson JS、Schuster SJ、Locke FL、Andreadis C
第一作者单位
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.United States
通讯作者单位
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.United States
文献类型
非美国政府资助研究 · 综述
期刊
American journal of hematology2021 Oct 1
原文标识
PubMed 34310745 · DOI 10.1002/ajh.26301