Pictured: FDA signage at its headquarters in Maryland/iStock, hapabapa

图为美国食品和药物管理局（FDA）位于马里兰州/伊斯托克（iStock，hapabapa）总部的标牌

The FDA announced on Thursday that it will officially require an update to the boxed warnings of CAR-T cell therapies, which should now also alert patients and prescribers to a heightened risk of developing secondary T cell malignancies.

FDA周四宣布，将正式要求更新CAR-T细胞疗法的盒装警告，现在还应该提醒患者和处方者发生继发性T细胞恶性肿瘤的风险增加。

All six commercially available CAR-T therapies will be affected, including Bristol Myers Squibb’s Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel), Novartis’ Kymriah (tisagenlecleucel), as well as Gilead’s Tecartus (brexucabtagene autoleucel) and Yecarta (axicabtagene ciloleucel)..

所有六种商业上可用的CAR-T疗法都将受到影响，包括百时美施贵宝的Abecma（idecabtagene-Vicluecel）和Breyanzi（Liscabtagene-Maraluecel），强生的Carvykti（ciltacabtagene-autoleucel），诺华的Kymriah（tisagenlecleucel），以及吉利德的Tecartus（brexucabtagene-autoleucel）和Yecarta（axicabtagene-ciloleucel）。。

The FDA will also mandate amendments to other sections of their labels, including the warnings and precautions, postmarketing experience, patient counseling information and medication guide sections.

FDA还将要求修改其标签的其他部分，包括警告和注意事项，上市后经验，患者咨询信息和药物指南部分。

Patients and clinical trial participants being given these products should also be followed “life-long” for the potential development of secondary T cell cancers, according to the regulator’s announcement.

根据监管机构的公告，服用这些产品的患者和临床试验参与者也应该“终身”关注继发性T细胞癌的潜在发展。

The FDA first revealed that it was looking into the potential safety issues of BCMA- or CD19-directed autologous CAR-T therapies in November 2023, noting at the time that it had flagged a “serious risk” of secondary T cell malignancies “in patients treated with several products in the class.” These cases were detected from both clinical trials and postmarket reporting..

FDA于2023年11月首次透露，它正在研究BCMA或CD19指导的自体CAR-T疗法的潜在安全性问题，当时指出，在使用该类产品治疗的患者中，它已经标记出继发性T细胞恶性肿瘤的“严重风险”。“这些病例是从临床试验和上市后报告中发现的。”。。

In January 2024, the regulator called on CAR-T manufacturers to implement a class-wide boxed warning to their products, reflecting the increased risk of secondary malignancies. In its letter to the companies, the FDA did not explicitly cite a causal link between the products and the adverse event, though it did note that the secondary cancers could lead to “serious outcomes, including hospitalization and death.”.

2024年1月，监管机构呼吁CAR-T制造商对其产品实施全类别盒装警告，反映出继发性恶性肿瘤的风险增加。在给这些公司的信中，FDA没有明确引用产品与不良事件之间的因果关系，尽管它确实指出继发性癌症可能导致“严重后果，包括住院和死亡”。

A few days later, two FDA officials published a perspective piece in The New England Journal of Medicine, revealing more details from its safety probe. The officials revealed they found the CAR transgene in three cases of secondary malignancies, indicating that “the CAR-T product was most likely involved in the development of the T-cell cancer.”.

几天后，两名FDA官员在《新英格兰医学杂志》上发表了一篇透视文章，揭示了其安全性调查的更多细节。官员们透露，他们在三例继发性恶性肿瘤中发现了CAR转基因，这表明“CAR-T产物很可能与T细胞癌的发展有关。”。

The FDA’s boxed warning announcement on Thursday comes as CAR-T cell therapies continue to break new ground, demonstrating their potential in more treatment settings and new indications.

美国食品和药物管理局（FDA）周四发布盒装警告声明之际，CAR-T细胞疗法继续取得新进展，证明其在更多治疗环境和新适应症方面的潜力。

In March 2024, the FDA greenlit BMS’ Breyanzi for the treatment of chronic lymphocytic leukemia and small lymphocytic leukemia, making it the first CAR-T therapy approved in these indications. Earlier this month, the regulator also cleared the use of BMS’ Abecma and J&J’s Carvykti in earlier lines of treatment for multiple myeloma..

2024年3月，FDA Greenlight BMS的Breyanzi用于治疗慢性淋巴细胞白血病和小淋巴细胞白血病，使其成为这些适应症中批准的第一种CAR-T疗法。本月早些时候，监管机构还批准在多发性骨髓瘤的早期治疗中使用BMS的Abecma和强生的Carvykti。。

Beyond cancer, CAR-T therapies have also shown promise in the treatment of autoimmune diseases. In February 2024, a small study published in The New England Journal of Medicine showed that CD19 CAR-T treatment could elicit strong clinical benefit in patients with systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myositis..

除癌症外，CAR-T疗法在治疗自身免疫性疾病方面也显示出前景。2024年2月，发表在《新英格兰医学杂志》上的一项小型研究表明，CD19 CAR-T治疗可以在系统性红斑狼疮，系统性硬化症和特发性炎性肌炎患者中产生强大的临床益处。。

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

特里斯坦·马纳拉克（TristanManalac）是一位独立的科学作家，总部位于菲律宾大马尼拉。在LinkedIn上联系他，或发电子邮件给他tristan@tristanmanalac.com或tristan.manalac@biospace.com.