Pictured: Johnson & Johnson's office in Spain/iStock, BrasilNut1, BMS sign on a building in San Diego, California/iStock, JHVEPhoto. Collage by Nicole Bean for BioSpace

图为强生公司在西班牙的办公室/巴西伊斯托克，BMS在加利福尼亚州圣地亚哥的一栋建筑上的标志/伊斯托克，JHVEPhoto。NicoleBean为BioSpace创作的拼贴画

The FDA has approved two CAR-T cell therapies for the earlier treatment of multiple myeloma. The first approval, for Bristol Myers Squibb and 2seventy Bio’s Abecma, came Friday morning, followed by that of Johnson & Johnson and Legend Biotech’s Carvykti on Friday evening.

FDA已批准两种CAR-T细胞疗法用于多发性骨髓瘤的早期治疗。周五上午，百时美施贵宝（Bristol-Myers Squibb）和2seventy Bio的Abecma获得了首次批准，随后，强生（Johnson＆Johnson）和联想生物科技（Legend Biotech）的Carvykti于周五晚间获得批准。

The approvals come three weeks after an FDA advisory committee unanimously recommended Carvykti as a second-line treatment for patients with refractory multiple myeloma, and backed Abecma by a vote of 8-3 for patients who had received at least two previous drug regimens. Carvykti joins seven other therapies that can be used as second-line treatments for multiple myeloma if initial therapies fail..

三周前，FDA咨询委员会一致建议Carvykti作为难治性多发性骨髓瘤患者的二线治疗药物，并以8比3的票数支持Abecma治疗至少接受过两种药物治疗的患者。Carvykti加入了其他七种疗法，如果初始疗法失败，这些疗法可以用作多发性骨髓瘤的二线治疗。。

Both Abecma and Carvykti reprogram a patient’s T-cells to eliminate cells that express B-cell maturation antigen (BCMA), which is present in normal B-cells but overexpressed in multiple myeloma.

Abecma和Carvykti均对患者的T细胞进行重编程，以消除表达B细胞成熟抗原（BCMA）的细胞，该抗原存在于正常B细胞中，但在多发性骨髓瘤中过表达。

While the FDA’s Oncologic Drugs Advisory Committee expressed concerns about higher rates of early deaths in the treatment arms of trials for both drugs, it ultimately determined that the benefits of the therapies outweighed the risks.

虽然FDA肿瘤药物咨询委员会对两种药物试验治疗组的早期死亡率较高表示担忧，但最终确定治疗的益处大于风险。

Prior to Friday’s approval, Abecma was authorized to treat patients with relapsed or refractory multiple myeloma in adult patients who have previously received four or more treatment regimens. It is the first CAR T cell therapy approved for earlier use for triple-class exposed relapsed and/or refractory multiple myeloma, according to BMS. .

在周五的批准之前，Abecma被授权治疗先前接受过四种或四种以上治疗方案的成年患者的复发或难治性多发性骨髓瘤患者。据BMS称，这是第一个被批准早期用于三级暴露复发和/或难治性多发性骨髓瘤的CAR T细胞疗法。

“Abecma has demonstrated a progression-free survival benefit three times that of standard regimens in relapsed or refractory multiple myeloma,” Bryan Campbell, senior vice president and head of commercial, cell therapy at BMS, said in a statement.

BMS高级副总裁兼商业、细胞治疗主管布莱恩·坎贝尔（BryanCampbell）在一份声明中表示：“Abecma在复发或难治性多发性骨髓瘤中显示出的无进展生存获益是标准方案的三倍。”。

In the Phase III KarMMa-3 trial, treatment with Abecma led to a 51% reduction in the risk of disease progression or death. Patients treated with the CAR-T therapy survived a median 13.3 months without progression, while those in the control group lived only 4.4 months without their disease advancing.

在III期KarMMa-3试验中，用Abecma治疗导致疾病进展或死亡风险降低51%。接受CAR-T治疗的患者平均存活13.3个月，无进展，而对照组患者仅存活4.4个月，无疾病进展。

Abecma’s safety profile was well-established, according to BMS, though the therapy does come with a boxed warning for cytokine release syndrome, neurologic toxicities, HLH/MAS, prolonged cytopenia and secondary hematologic malignancies..

据BMS称，Abecma的安全性已经确立，尽管该疗法确实对细胞因子释放综合征，神经系统毒性，HLH/MAS，长期血细胞减少症和继发性血液系统恶性肿瘤发出了盒装警告。。

The FDA nod comes three weeks after the European Commission authorized Abecma for the third-line treatment of multiple myeloma.

三周前，欧盟委员会批准阿贝克玛用于多发性骨髓瘤的三线治疗。

Carvykti Wins Second Line Nod

Carvykti赢得二线点头

Carvykti, which won expanded approval late Friday evening, is the first BCMA-Targeted therapy for the second-line treatment of multiple myeloma, according to Legend Biotech.

Legend Biotech称，Carvykti是第一个用于多发性骨髓瘤二线治疗的BCMA靶向疗法，于周五晚间获得扩大批准。

The CAR-T cell therapy is authorized for patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent and are refractory to lenalidomide.

CAR-T细胞疗法被授权用于接受至少一种先前治疗方案（包括蛋白酶体抑制剂和免疫调节剂）且对来那度胺难治的患者。

J&J and Legend Biotech supported their application with data from the  CARTITUDE-4 study, where treatment with Carvykti led to 'statistically significant and clinically meaningful improvement of progression-free survival compared to two standard of care treatment regimens,' according to the companies. .

强生和联想生物技术公司（Legend Biotech）利用Cartitute-4研究的数据支持了他们的应用，据该公司称，Carvykti治疗导致“与两种标准治疗方案相比，无进展生存率具有统计学意义和临床意义的改善”。。

Carvykti was also tagged with a boxed warning for potential side effects, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and secondary malignancies, including myelodysplastic syndrome, acute myeloid leukemia and T-cell cancers.

Carvykti还被标记为潜在副作用的盒装警告，包括细胞因子释放综合征，免疫效应细胞相关神经毒性综合征和继发性恶性肿瘤，包括骨髓增生异常综合征，急性髓细胞白血病和T细胞癌。

The therapy was originally approved in February 2022 as a fifth-line treatment. It was also conditionally approved in Europe for patients who had tried at least three other therapies. The European Medicines Agency’s Committee for Medicinal Products for Human Use recently supported approving Carvykti as a second-line treatment for multiple myeloma..

该疗法最初于2022年2月被批准为第五线治疗。欧洲也有条件地批准了至少尝试过三种其他疗法的患者。欧洲药品管理局（European Medicines Agency）的人用药品委员会（Committee for Medical Products for Human Use）最近支持批准Carvykti作为多发性骨髓瘤的二线治疗药物。。

The FDA has demonstrated caution toward CAR-T therapies in recent months. In November 2023, the agency began investigating the “serious risk” of T-cell malignancies in patients treated with BCMA- or CD19-directed autologous CAR-T cell immunotherapies. In January 2024, the FDA called for boxed warnings for all currently marketed CAR-T therapies after three of 22 cases were found to have likely causal links.

近几个月来，FDA对CAR-T疗法表现出谨慎态度。2023年11月，该机构开始调查接受BCMA或CD19定向自体CAR-T细胞免疫疗法治疗的患者T细胞恶性肿瘤的“严重风险”。2024年1月，在发现22例病例中有3例可能存在因果关系后，FDA呼吁对所有目前上市的CAR-T疗法发出盒装警告。

However, the regulator stated that the overall risk of T-cell cancers in people receiving CAR-T therapies “appears to be quite low.”.

然而，监管机构表示，接受CAR-T治疗的人患T细胞癌的总体风险“似乎相当低”。

Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.

希瑟·麦肯齐是BioSpace的高级编辑。你可以通过heather.mckenzie@biospace.com.也可以在LinkedIn上关注她。

Nadia Bey is a freelance reporter from North Carolina. Her work and contact information are available at nadiabey.com.

NadiaBey是来自北卡罗莱纳州的自由撰稿人。她的工作和联系方式可以在nadiabey.com上找到。