Risk factors for CAR‐T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

• DOI: 10.1111/bjh.18831
• Publication Date: 2023-04-25T12:45:47Z
• 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‐Fuj...; 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‐I...; Ryuji Tanosaki; Yasuyuki Arai
• Keywords: Receptors, Chimeric Antigen; T-Lymphocytes; Receptors, Antigen, T-Cell; chimeric antigen receptor T cell therapy; Immunotherapy, Adoptive; 3. Good health; Cohort Studies; tisagenlecleucel; Japan; manufacturing failure; Risk Factors; Humans; Bendamustine Hydrochloride; Lymphoma, Large B-Cell, Diffuse

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 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 between 30 cases that failed (7.4%) those succeeded ( n = 378). Among the failures, proportion of previously treated bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, their platelet counts (12.0 17.0 × 10 4 /μL; 0.01) CD4/CD8 T‐cell ratio (0.30 0.56; peripheral blood at apheresis were lower than group. Multivariate analysis revealed repeated use short washout periods prior (odds [OR], 5.52; 0.013 ≥6 cycles period 3–24 months; OR, 57.09; 0.005 ≥3 <3 months), low (OR, 0.495 per 5 0.022) or ratios (<one third) 3.249; 0.011) increased failure. Manufacturing remains an obstacle therapy DLBCL patients. Avoiding factors, such as administration sufficient washout, risk‐adapted strategies may help optimize