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CAR-T 细胞治疗后继发性恶性肿瘤的当前格局:如何预防恶性肿瘤?

英文原题:The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?

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The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?

PubMed 2024/09/01(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法通过在高度难治性血液恶性肿瘤患者中实现令人瞩目的缓解率并改善总生存期,彻底改变了血液恶性肿瘤领域。迄今为止,美国食品药品监督管理局(FDA)已批准六种商业化抗CD19和抗BCMA CAR-T 细胞产品,用于治疗复发/难治性B细胞血液恶性肿瘤和多发性骨髓瘤。CAR-T 细胞疗法的适应症正在逐步扩大,这些疗法正在多种疾病中进行研究,包括非恶性疾病。尽管取得了巨大成功,但CAR-T 细胞疗法仍面临若干挑战,例如缓解不持久和高级别毒性。

此外,在2023年11月28日,FDA在收到既往接受过抗CD19或抗BCMA自体CAR-T 细胞治疗的患者在临床试验和真实世界环境中出现T细胞恶性肿瘤的报告后,新增了一项安全性担忧。此后,已有多篇报告发表,呈现了CAR-T 细胞治疗后其他第二原发恶性肿瘤的发生率并分析了其风险。在这篇观点文章中,我们呈现了CAR-T 细胞治疗后第二原发恶性肿瘤的当前格局,并提出了一种未来研究策略,旨在潜在减少或消除CAR-T 细胞治疗后发生第二原发恶性肿瘤的风险。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory haematological malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR T-cell products have been approved by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory B-cell haematological malignancies and multiple myeloma.

The indications for CAR T-cell therapies are gradually expanding, with these therapies being investigated in a variety of diseases, including non-malignant ones. Despite the great success, there are several challenges surrounding CAR T-cell therapies, such as non-durable responses and high-grade toxicities.

In addition, a new safety concern was added by the FDA on 28 November 2023 following reports of T-cell malignancies in patients previously treated with either anti-CD19 or anti-BCMA autologous CAR T-cell therapies both in clinical trials and in the real-world setting. Since then, several reports have been published presenting the incidence and analysing the risks of other secondary malignancies after CAR T-cell therapies.

In this opinion article, the current landscape of secondary malignancies after CAR T-cell therapies is presented, along with a proposed strategy for future research aiming at potentially diminishing or abrogating the risk of developing secondary malignancies after CAR T-cell therapies.

论文信息

作者
Bouziana S、Bouzianas D
第一作者单位
Department of Hematology, King's College Hospital, London SE59RS, UK.United Kingdom
通讯作者单位
BReMeL, Biopharmaceutical and Regenerative Medicine Laboratories, 55534 Thessaloniki, Greece.Greece
文献类型
综述
期刊
International journal of molecular sciences2024 Sep 1
原文标识
PubMed 39273462 · DOI 10.3390/ijms25179518