Pictured: Entrance to the FDA's office in Maryland/iStock, Grandbrothers

图为美国食品和药物管理局驻马里兰州/伊斯托克办公室入口

The FDA is currently looking into at least 22 cases of secondary malignancies in patients after receiving CAR-T therapies, according to a perspective piece from two agency officials published Wednesday in The New England Journal of Medicine.

根据周三在《新英格兰医学杂志》上发表的两位机构官员的观点，FDA目前正在调查接受CAR-T治疗后至少22例继发性恶性肿瘤患者。

The cases were detected as of the end of 2023, according to Peter Marks and Nicole Verdun, both from the FDA’s Center for Biologics Evaluation and Research (CBER). Fourteen secondary malignancies have “adequate data” available for analysis, all of which arose within two years after CAR-T treatment, while “roughly half” within a year of administration..

根据来自FDA生物制剂评估与研究中心（CBER）的彼得·马克斯（PeterMarks）和妮可·凡尔登（NicoleVerdun）的数据，这些病例是在2023年底被发现的。十四种继发性恶性肿瘤有“足够的数据”可供分析，所有这些都是在CAR-T治疗后两年内出现的，而在给药后一年内“大约一半”。。

The secondary cancers include T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

继发性癌症包括T细胞淋巴瘤，T细胞大颗粒淋巴细胞增多症，外周T细胞淋巴瘤和皮肤T细胞淋巴瘤。

In three cases, genetic sequencing data found the CAR transgene in a malignant clone, suggesting that “the CAR-T product was most likely involved in the development of the T-cell cancer,” Marks and Verdun wrote.

在三个案例中，基因测序数据在恶性克隆中发现了CAR转基因，这表明“CAR-T产物最有可能参与T细胞癌的发展，”Marks和Verdun写道。

Wednesday’s NEJM perspective piece follows the FDA’s push last week for a class-wide boxed warning on all commercial CAR-T therapies. The agency sent out similarly worded letters to CAR-T manufacturers, directing them to adjust their respective products’ labels to reflect the potential risk of secondary T-cell cancers.

周三的《NEJM透视图》报道了美国食品和药物管理局（FDA）上周发布的关于所有商业CAR-T疗法的全类盒装警告。该机构向CAR-T制造商发出了措辞类似的信件，指示他们调整各自产品的标签，以反映继发性T细胞癌的潜在风险。

The FDA first revealed that it had detected these potential risks in November 2023, launching a probe into the safety of the CAR-T class..

美国食品和药物管理局（FDA）于2023年11月首次透露，它已经发现了这些潜在风险，并对CAR-T级的安全性展开了调查。。

The boxed warnings were to affect all six commercially available CAR-T products, including Gilead’s Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel), BMs’s Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Novartis’ Kymriah (tisagenlecleucel) and J&J’s Carvykti (ciltacabtagene autoleucel)..

盒装警告将影响所有六种商用CAR-T产品，包括吉利德的Yescarta（axicabtagene ciloleucel）和Tecartus（brexucabtagene autoleucel）、BMs的Abecma（idecabtagene Vicluel）和Breyanzi（Liscabtagene Maraluel）、诺华的Kymriah（tisagenlecleucel）和强生的Carvykti（ciltacabtagene autoleucel）。。

According to the NEJM article, cases of secondary T-cell malignancies have been documented for “five of the six available CAR-T products,” though they did not name a specific product. Instead, the authors noted that the agency still does not have enough data to draw definitive conclusions “about the strength of an association with any specific product.”.

根据NEJM的文章，已经记录了“六种可用的CAR-T产品中的五种”继发性T细胞恶性肿瘤的病例，尽管他们没有指定特定的产品。相反，作者指出，该机构仍然没有足够的数据来“关于与任何特定产品的关联强度”得出明确的结论。

The FDA officials are also quick to emphasize in their article that “the overall rate of T-cell cancers among people receiving CAR-T therapies appears to be quite low, even if all reported cases are assumed to be related to treatment.” So far, over 27,000 doses of the six approved CAR-T products have been administered throughout the U.S..

FDA官员也很快在他们的文章中强调，“接受CAR-T治疗的人群中T细胞癌的总体发病率似乎很低，即使所有报告的病例都被认为与治疗有关。”到目前为止，美国已经服用了超过27000剂六种经批准的CAR-T产品。。

Still, relying solely on post-marketing surveillance could underestimate these secondary cancers, according to Marks and Verdun, who assert that adjusting the products’ labels to appropriately reflect these risks will help physicians better communicate the benefits and potential downsides of CAR-T treatment with their patients..

尽管如此，根据Marks和Verdun的说法，仅仅依靠上市后监测可能会低估这些继发性癌症，他们声称调整产品标签以适当反映这些风险将有助于医生更好地与患者沟通CAR-T治疗的益处和潜在缺点。。

Marks and Verdun recommended that physicians monitor CAR-T patients, including those who received the therapy during a clinical trial, for new cancers for the lifetime of the patients and asked clinicians to report any new malignancies in their patients to the FDA.

Marks和Verdun建议医生监测CAR-T患者，包括在临床试验期间接受治疗的患者，在患者的一生中监测新的癌症，并要求临床医生向FDA报告患者的任何新的恶性肿瘤。

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached 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，总部位于菲律宾马尼拉。联系方式tristan@tristanmanalac.com或tristan.manalac@biospace.com.