PMID- 36399286
OWN - NLM
STAT- MEDLINE
DCOM- 20230301
LR  - 20230301
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 117
IP  - 3
DP  - 2023 Mar
TI  - A phase 2 study of axicabtagene ciloleucel in relapsed or refractory large B-cell 
      lymphoma in Japan: 1-year follow-up and biomarker analysis.
PG  - 409-420
LID - 10.1007/s12185-022-03494-7 [doi]
AB  - Axicabtagene ciloleucel (axi-cel) is an autologous, CD19-targeting chimeric 
      antigen receptor T‑cell therapy. We recently reported the 3-month follow-up 
      results of a phase 2, multicenter, open‑label, single-arm study of axi-cel in 
      Japanese patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) 
      (JapicCTI-183914). Here, we present 1-year efficacy and safety data and biomarker 
      analysis data regarding mechanisms of resistance to axi-cel. Primary and 
      secondary endpoints included investigator-assessed objective response rate (ORR), 
      serious adverse events, and treatment-emergent adverse events. Axi-cel 
      pharmacokinetics were also examined. Biomarker analysis was performed by cytokine 
      measurement, immunohistochemistry, RNA sequencing, and whole-exome sequencing. At 
      a median follow-up of 13.4 months, ORR was 86.7% (13/15 patients), and the 
      complete response (CR) rate improved to 53.3% (8/15 patients) due to response 
      conversion. Seven patients experienced disease progression, and one achieved CR 
      after re-treatment with axi-cel. No new safety concerns were detected. Plausible 
      resistance mechanisms to axi-cel varied among patients but included CD19 
      downregulation, programmed death-ligand 1 upregulation, and increased macrophage 
      and angiogenesis signatures. The 1-year efficacy and safety of axi-cel were 
      confirmed in Japanese patients with R/R LBCL. Resistance to treatment may involve 
      multiple factors, including target antigen loss and an unfavorable tumor 
      environment.Clinical trial registration: Japan Clinical Trials Information; 
      JapicCTI-183914.
CI  - (c) 2022. Japanese Society of Hematology.
FAU - Kato, Koji
AU  - Kato K
AUID- ORCID: 0000-0002-5815-4585
AD  - Department of Medicine and Biosystemic Science, Kyushu University Graduate School 
      of Medical Sciences, 3-1-1 Maidashi, Fukuoka Higashi-ku, Fukuoka, 812-8582, 
      Japan. kato.koji.429@m.kyushu-u.ac.jp.
FAU - Fujii, Nobuharu
AU  - Fujii N
AD  - Department of Hematology and Oncology, Okayama University Hospital, Okayama, 
      Japan.
FAU - Makita, Shinichi
AU  - Makita S
AD  - Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
FAU - Goto, Hideki
AU  - Goto H
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, 
      Japan.
FAU - Kanda, Junya
AU  - Kanda J
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Japan.
FAU - Shimada, Kazuyuki
AU  - Shimada K
AD  - Department of Hematology and Oncology, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Akashi, Koichi
AU  - Akashi K
AD  - Department of Medicine and Biosystemic Science, Kyushu University Graduate School 
      of Medical Sciences, 3-1-1 Maidashi, Fukuoka Higashi-ku, Fukuoka, 812-8582, 
      Japan.
FAU - Izutsu, Koji
AU  - Izutsu K
AD  - Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
FAU - Teshima, Takanori
AU  - Teshima T
AD  - Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, 
      Japan.
FAU - Fukuda, Natsuko
AU  - Fukuda N
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Sumitani, Tokuhito
AU  - Sumitani T
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Nakamura, Shota
AU  - Nakamura S
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Sumi, Hiroyuki
AU  - Sumi H
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Shimizu, Shinji
AU  - Shimizu S
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Kakurai, Yasuyuki
AU  - Kakurai Y
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Yoshikawa, Kenji
AU  - Yoshikawa K
AD  - Daiichi Sankyo Co., Ltd., Tokyo, Japan.
FAU - Tobinai, Kensei
AU  - Tobinai K
AD  - Geriatric Health Services Facility Rehabilitation Care Funabashi, Chiba, Japan.
FAU - Usui, Noriko
AU  - Usui N
AD  - Department of Clinical Oncology and Hematology, The Jikei University Daisan 
      Hospital, Tokyo, Japan.
FAU - Hatake, Kiyohiko
AU  - Hatake K
AD  - Department of Lymphoma/Hematology Center, Mita Hospital, International University 
      of Health and Welfare, Tokyo, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20221118
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - U2I8T43Y7R (axicabtagene ciloleucel)
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Humans
MH  - Follow-Up Studies
MH  - Japan
MH  - *Immunotherapy, Adoptive/adverse effects/methods
MH  - *Lymphoma, Large B-Cell, Diffuse/therapy/pathology
MH  - Antigens, CD19/therapeutic use
OTO - NOTNLM
OT  - Axi-cel
OT  - Biomarker
OT  - CAR T cell
OT  - Clinical trial
OT  - Relapsed or refractory large B-cell lymphoma
EDAT- 2022/11/19 06:00
MHDA- 2023/03/03 06:00
CRDT- 2022/11/18 11:17
PHST- 2022/07/21 00:00 [received]
PHST- 2022/11/08 00:00 [accepted]
PHST- 2022/11/08 00:00 [revised]
PHST- 2022/11/19 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2022/11/18 11:17 [entrez]
AID - 10.1007/s12185-022-03494-7 [pii]
AID - 10.1007/s12185-022-03494-7 [doi]
PST - ppublish
SO  - Int J Hematol. 2023 Mar;117(3):409-420. doi: 10.1007/s12185-022-03494-7. Epub 
      2022 Nov 18.