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利妥昔单抗注射用偶联剂治疗复发或难治性弥漫性大 B 细胞淋巴瘤:有何证据?

Lisocabtagene Maraleucel in Relapsed or Refractory Diffuse Large B Cell Lymphoma: What is the Evidence?

机构信息

Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Programs, Mayo Clinic, Jacksonville, FL, USA.

出版信息

Hematol Oncol Stem Cell Ther. 2022 Dec 23;15(4):168-175. doi: 10.1016/j.hemonc.2021.09.004.

Abstract

Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T cell product, with a CD3ζ activatory domain connected to 4-1BB costimulatory domain. Liso-cel, unlike the other two approved products-axicabtagene ciloleucel and tisagenlecleucel-is manufactured separately from CD4 and CD8 T cells and then administered as a sequential infusion of the two components at equal target doses. The approval of liso-cel was based on the results of Transcend NHL 001, a single-arm, open-label, multicenter, seamless design trial that enrolled 344 patients, of whom 269 received conforming liso-cel. The most common histology was diffuse large B cell lymphoma, not otherwise specified (DLBCL NOS; n = 137, 51%) followed by DLBCL transformed from indolent lymphomas (n = 78, 29%). Encouraging results were reported, yielding an objective response rate across all dose levels of 73% [complete remission (CR) = 53%], with an estimated duration of response at 1 year of 55% for all patients and 65% for those achieving a CR. The estimated 12-month overall survival was 58% for all patients and 86% for those achieving a CR. Cytokine release syndrome and neurological adverse events were reported in 42% and 30%, respectively. This review summarizes the evidence on the safety and effectiveness of liso-cel, resulting in its addition to the current treatment armamentarium of relapsed or refractory large B cell lymphoma.

摘要

利妥昔单抗注射用细胞(liso-cel)是一种自体 CD19 导向嵌合抗原受体(CAR)T 细胞产品,其 CD3ζ 激活结构域与 4-1BB 共刺激结构域相连。与另外两种已获批的产品——axicabtagene ciloleucel 和 tisagenlecleucel 不同,liso-cel 是在分别从 CD4 和 CD8 T 细胞中制造出来的,然后以相等靶剂量的两种成分序贯输注的方式给药。liso-cel 的获批是基于 Transcend NHL 001 研究的结果,这是一项单臂、开放标签、多中心、无缝设计的临床试验,共纳入 344 例患者,其中 269 例接受了符合条件的 liso-cel 治疗。最常见的组织学类型是弥漫性大 B 细胞淋巴瘤,非特指型(DLBCL NOS;n = 137,51%),其次是惰性淋巴瘤转化而来的 DLBCL(n = 78,29%)。报告了令人鼓舞的结果,在所有剂量水平上的客观缓解率均为 73%[完全缓解(CR)= 53%],所有患者的缓解持续时间估计为 1 年时为 55%,CR 患者为 65%。所有患者的估计 12 个月总生存率为 58%,CR 患者为 86%。分别有 42%和 30%的患者报告发生细胞因子释放综合征和神经毒性不良事件。本文综述了 liso-cel 的安全性和有效性证据,这使其成为复发或难治性大 B 细胞淋巴瘤现有治疗方法的补充。

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