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

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

doi:10.1016/j.jtct.2024.11.016

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

Transplant Cell Ther. 2024 Nov 30:S2666-6367(24)00799-1. doi: 10.1016/j.jtct.2024.11.016. Online ahead of print.

Authors

Itaru Kato¹, Daisuke Tomizawa², Motohiro Kato³, Shinsuke Hirabayashi⁴, Atsushi Manabe⁴, Masahiro Irie⁵, Yoji Sasahara⁵, Yuki Arakawa⁶, Katsuyoshi Koh⁶, Hirotoshi Sakaguchi², Masanaka Sugiyama⁷, Chitose Ogawa⁷, Takahiro Kamiya⁸, Shoji Saito⁹, Yozo Nakazawa⁹, Nobuhiro Nishio¹⁰, Yoshiyuki Takahashi¹⁰, Naoko Iwai¹¹, Souichi Adachi¹², Junko Takita¹¹, Takako Miyamura¹³, Satomi Yokoyama¹⁴, Utako Oba¹⁴, Tamaki Ueda¹⁴, Yuhki Koga¹⁵, Hidefumi Hiramatsu¹¹

Affiliations

¹ Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: itarkt@kuhp.kyoto-u.ac.jp.
² Children's Cancer Center, National Center for Child Health and Development, Tokyo.
³ Children's Cancer Center, National Center for Child Health and Development, Tokyo; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
⁵ Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
⁶ Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
⁷ Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁸ Department of Pediatrics, Institute of Science Tokyo, Tokyo, Japan.
⁹ Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
¹⁰ Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹¹ Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹² Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹³ Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
¹⁴ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹⁵ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Pediatrics, Kindai University Faculty of Medicine, Osakasayama, Japan.

PMID: 39617098
DOI: 10.1016/j.jtct.2024.11.016

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.

Keywords: B cell acute lymphoblastic leukemia; CAR-T cell therapy; Children, adolescents, and young adults; Real-world outcomes.