TY - JOUR
T1 - Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia
T2 - First-in-Human, Phase I Trial
AU - Pan, Jing
AU - Tan, Yue
AU - Wang, Guoling
AU - Deng, Biping
AU - Ling, Zhuojun
AU - Song, Weiliang
AU - Seery, Samuel
AU - Zhang, Yanlei
AU - Peng, Shuixiu
AU - Xu, Jinlong
AU - Duan, Jiajia
AU - Wang, Zelin
AU - Yu, Xinjian
AU - Zheng, Qinlong
AU - Xu, Xiuwen
AU - Yuan, Ying
AU - Yan, Fangrong
AU - Tian, Zhenglong
AU - Tang, Kaiting
AU - Zhang, Jiecheng
AU - Chang, Alex H.
AU - Feng, Xiaoming
N1 - Funding Information:
Supported by the National Key R&D Program of China (2019YFA0110200), the Tianjin Science Funds for Distinguished Young Scholars (17JCJQJC45800), the CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-1-003), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32034, 2019-RC-HL-013).
Publisher Copyright:
Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2021/10/20
Y1 - 2021/10/20
N2 - PURPOSE Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have few options and poor prognosis. The aim was to assess donor-derived anti-CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-ALL. METHODS In this single-center, phase I trial, we administered anti-CD7 CAR T cells, manufactured from either previous stem-cell transplantation donors or new donors, to patients with r/r T-ALL, in single infusions at doses of 5 3 105 or 1 3 106 (630%) cells per kilogram of body weight. The primary end point was safety with efficacy secondary. RESULTS Twenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n 5 18) and grade 3-4 in 10% (n 5 2), cytopenia grade 3-4 in 100% (n 5 20), neurotoxicity grade 1-2 in 15% (n 5 3), graft-versus-host disease grade 1-2 in 60% (n 5 12), and viral activation grade 1-2 in 20% (n 5 4). All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months, postinfusion. Ninety percent (n 5 18) achieved complete remission with seven patients proceeding to stem-cell transplantation. At a median follow-up of 6.3 months (range, 4.0-9.2), 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion. Although patients’ CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency. CONCLUSION Among 20 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress (NCT04689659).
AB - PURPOSE Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have few options and poor prognosis. The aim was to assess donor-derived anti-CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-ALL. METHODS In this single-center, phase I trial, we administered anti-CD7 CAR T cells, manufactured from either previous stem-cell transplantation donors or new donors, to patients with r/r T-ALL, in single infusions at doses of 5 3 105 or 1 3 106 (630%) cells per kilogram of body weight. The primary end point was safety with efficacy secondary. RESULTS Twenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n 5 18) and grade 3-4 in 10% (n 5 2), cytopenia grade 3-4 in 100% (n 5 20), neurotoxicity grade 1-2 in 15% (n 5 3), graft-versus-host disease grade 1-2 in 60% (n 5 12), and viral activation grade 1-2 in 20% (n 5 4). All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months, postinfusion. Ninety percent (n 5 18) achieved complete remission with seven patients proceeding to stem-cell transplantation. At a median follow-up of 6.3 months (range, 4.0-9.2), 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion. Although patients’ CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency. CONCLUSION Among 20 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress (NCT04689659).
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U2 - 10.1200/JCO.21.00389
DO - 10.1200/JCO.21.00389
M3 - Article
C2 - 34324392
AN - SCOPUS:85115759487
SN - 0732-183X
VL - 39
SP - 3340
EP - 3351
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -