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日本商业用替沙格赛定治疗儿童、青少年和青年急性淋巴细胞白血病的真实世界结果

Real-world Outcomes of Commercial Tisagenlecleucel for Children, Adolescents, and Young Adults With Acute Lymphoblastic Leukemia in Japan.

作者信息

Kato Itaru, Tomizawa Daisuke, Kato Motohiro, Hirabayashi Shinsuke, Manabe Atsushi, Irie Masahiro, Sasahara Yoji, Arakawa Yuki, Koh Katsuyoshi, Sakaguchi Hirotoshi, Sugiyama Masanaka, Ogawa Chitose, Kamiya Takahiro, Saito Shoji, Nakazawa Yozo, Nishio Nobuhiro, Takahashi Yoshiyuki, Iwai Naoko, Adachi Souichi, Takita Junko, Miyamura Takako, Yokoyama Satomi, Oba Utako, Ueda Tamaki, Koga Yuhki, Hiramatsu Hidefumi

机构信息

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Children's Cancer Center, National Center for Child Health and Development, Tokyo.

出版信息

Transplant Cell Ther. 2025 Feb;31(2):86-96. doi: 10.1016/j.jtct.2024.11.016. Epub 2024 Nov 30.

Abstract

Chimeric antigen receptor (CAR) T cells are a major new treatment option for children, adolescents, and young adults (CAYA) patients with relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Therefore, accumulating evidence from real-world experiences of CAR-T outcomes in various regions worldwide is important, particularly when comparing outcomes of patients with differing medical and ethnic backgrounds. More than 5 years have passed since tisagenlecleucel was approved in Japan. Here, we report a retrospective, multi-institutional investigation examining the association between baseline parameters and clinical outcomes. The aim was to investigate real-world experience and to better comprehend the efficacy of commercial tisagenlecleucel. A nationwide consortium called the Japan CAR-T Consortium conducted a retrospective, multicenter study of CAYA patients who received CAR-T cell treatment with commercial tisagenlecleucel. Forty-two patients with R/R B-ALL whose leukapheresis samples were shipped to Novartis for commercial tisagenlecleucel manufacture were included in the analysis. All infused patients were included in the response, toxicity, and survival analyses. The best overall response rate was 93%. The 1-year overall survival and event-free survival (EFS) rates after infusion were 82% and 56%, respectively. Twenty-seven (64%) had low disease burden (LB, defined as <5% bone marrow [BM] lymphoblasts) prior to tisagenlecleucel infusion. LB was associated with superior outcomes, with a 1-year EFS rate of 80% compared with 24% in high disease burden (≧5% BM lymphoblasts). Multivariate analysis identified an association between prior hematopoietic stem cell transplantation (HSCT) (n = 23, 55%) and superior outcomes, with a 1-year EFS rate of 75% compared with 24% for patients without prior HSCT. This first analysis of CAYA patients with R/R B-ALL undergoing treatment with commercial tisagenlecleucel in Japan reports an efficacy similar to that in clinical trials and other real-world studies and confirms that LB and prior HSCT are associated with superior EFS.

摘要

嵌合抗原受体(CAR)T细胞是复发难治性(R/R)B细胞急性淋巴细胞白血病(B-ALL)的儿童、青少年和青年(CAYA)患者的一种重要新治疗选择。因此,积累全球各地区CAR-T治疗结果的真实世界经验证据很重要,尤其是在比较不同医学和种族背景患者的治疗结果时。自tisagenlecleucel在日本获批以来已过去5年多时间。在此,我们报告一项回顾性、多机构调查,研究基线参数与临床结果之间的关联。目的是调查真实世界经验并更好地理解商业化tisagenlecleucel的疗效。一个名为日本CAR-T联盟的全国性联合体对接受商业化tisagenlecleucel CAR-T细胞治疗的CAYA患者进行了一项回顾性、多中心研究。分析纳入了42例R/R B-ALL患者,其白细胞分离样本被送往诺华用于商业化tisagenlecleucel生产。所有输注患者均纳入缓解、毒性和生存分析。最佳总缓解率为93%。输注后1年总生存率和无事件生存率(EFS)分别为82%和56%。27例(64%)患者在tisagenlecleucel输注前疾病负担较低(LB,定义为骨髓[BM]原始淋巴细胞<5%)。LB与更好的治疗结果相关,1年EFS率为80%,而高疾病负担(≧5% BM原始淋巴细胞)患者为24%。多变量分析确定既往造血干细胞移植(HSCT)(n = 23,55%)与更好的治疗结果相关,既往未接受HSCT患者的1年EFS率为24%,而接受过HSCT患者为75%。这项对日本接受商业化tisagenlecleucel治疗的R/R B-ALL CAYA患者的首次分析报告了与临床试验和其他真实世界研究相似的疗效,并证实LB和既往HSCT与更好的EFS相关。

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