Department of Hematology, King's College Hospital, London SE59RS, UK.
BReMeL, Biopharmaceutical and Regenerative Medicine Laboratories, 55534 Thessaloniki, Greece.
Int J Mol Sci. 2024 Sep 1;25(17):9518. doi: 10.3390/ijms25179518.
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.
嵌合抗原受体 (CAR) T 细胞疗法通过在难治性血液系统恶性肿瘤患者中实现令人印象深刻的缓解率,改善总体生存率,彻底改变了血液系统恶性肿瘤的治疗领域。迄今为止,已有六种抗 CD19 和抗 BCMA CAR T 细胞产品获得美国食品和药物管理局 (FDA) 的批准,用于治疗复发/难治性 B 细胞血液系统恶性肿瘤和多发性骨髓瘤。CAR T 细胞疗法的适应证正在逐渐扩大,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 细胞疗法仍存在一些挑战,如反应不可持续和高等级毒性。此外,在临床试验和真实环境中,接受抗 CD19 或抗 BCMA 自体 CAR T 细胞治疗的患者出现 T 细胞恶性肿瘤的报告后,FDA 于 2023 年 11 月 28 日增加了一个新的安全问题。此后,已经发表了几篇报告,介绍了 CAR T 细胞治疗后其他继发性恶性肿瘤的发生率,并对其风险进行了分析。在这篇观点文章中,介绍了 CAR T 细胞治疗后继发性恶性肿瘤的现状,并提出了一项未来研究的策略,旨在潜在地降低或消除 CAR T 细胞治疗后发生继发性恶性肿瘤的风险。