Risk factors for CAR‐T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan
Year: 2023
Type: article
Study design: Observational Study
Abstract: Summary For successful chimeric antigen receptor T (CAR‐T) cell therapy, CAR‐T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR‐T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B‐cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded ( n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10 4 /μL; p = 0.01) and CD4/CD8 T‐cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 10 5 /μL; p = 0.022) or low CD4/CD8 ratios (<one third) (OR, 3.249; p = 0.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR‐T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk‐adapted strategies may help to optimize CAR‐T cell therapy for DLBCL patients.
Source: British Journal of Haematology
DOI: 10.1111/bjh.18831
Authors: Tomoyasu Jo, Satoshi Yoshihara, Yoshiki Okuyama, Keiko Fujii, Tomoko Henzan, Kaoru Kahata, Rie Yamazaki, Wataru Takeda, Yoshihiro Umezawa, Kentaro Fukushima, Takashi Ashida, Minami Yamada‐Fujiwara, Ryo Hanajiri, Noboru Yonetani, Yuma Tada, Yuji Shimura, Hidekazu Nishikii, Norio Shiba, Naoya Mimura, Jun Ando, Takayuki Sato, Yasuhiro Nakashima, Junko Ikemoto, Keita Iwaki, Shin‐ichiro Fujiwara, Masaki Ri, Tokiko Nagamura‐Inoue, Ryuji Tanosaki, Yasuyuki Arai
Institutions: Kyoto University Hospital, Hyogo Medical University Hospital, Tokyo Metropolitan Komagome Hospital, Okayama University Hospital, Kyushu University, Kyushu University Hospital, Hokkaido University, Keio University, National Cancer Center Hospital, Tokyo Medical and Dental University, The University of Osaka, Kindai University Hospital, Tohoku University Hospital, Nagoya University, Kobe Medical Center, Kobe City Medical Center General Hospital, Osaka International Cancer Institute, Kyoto Prefectural University of Medicine, University Hospital Kyoto Prefectural University of Medicine, University of Tsukuba, Yokohama City University, Chiba University Hospital, Juntendo University, Kurashiki Central Hospital, Osaka Metropolitan University, Jichi Medical University Hospital, Nagoya City University, Institute of Medical Science, The University of Tokyo, The University of Tokyo
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,940
Awards: Development of a Novel Experimental Model for B-cell Lymphoma and Identification of Novel Therapeutic Targets, CRISPR screening of B-cell lymphoma to enhance CAR-T therapy, Adoptive immunotherapy for adult T-cell leukemia/lymphoma with ex vivo expanded multi-tumor associated antigen specific cytotoxic T-cells
OpenAlex ID: W4366985169