Jing Pan1, Yue Tan2, Guoling Wang2, Biping Deng3, Zhuojun Ling4, Weiliang Song4, Samuel Seery5,6, Yanlei Zhang7, Shuixiu Peng7, Jinlong Xu4, Jiajia Duan4, Zelin Wang4, Xinjian Yu8, Qinlong Zheng8, Xiuwen Xu8, Ying Yuan9, Fangrong Yan10, Zhenglong Tian11, Kaiting Tang4, Jiecheng Zhang12, Alex H Chang7,13, Xiaoming Feng2,14. 1. State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Boren Hospital, Beijing, China. 2. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin China. 3. Cytology Laboratory, Beijing Boren Hospital, Beijing, China. 4. Department of Hematology, Beijing Boren Hospital, Beijing, China. 5. School of Humanities and Social Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 6. Faculty of Health and Medicine, Division of Health Research, Lancaster University, Lancaster, United Kingdom. 7. Shanghai YaKe Biotechnology Ltd, Shanghai, China. 8. Medical Laboratory, Beijing Boren Hospital, Beijing, China. 9. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, TX. 10. Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Longmian Avenue, Nanjing, China. 11. Gobroad Research Center, Gobroad Medical Group, Beijing, China. 12. Department of Hospital Management, Gobroad Medical Group, Beijing, China. 13. Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 14. Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.
Abstract
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 × 105 or 1 × 106 (±30%) 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 = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 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 = 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).
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 × 105 or 1 × 106 (±30%) 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 = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 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 = 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).
Authors: Lianqun Qiu; L Jeffrey Medeiros; Guilin Tang; Mahsa Khanlari; Shaoying Li; Sergej Konoplev; Sa A Wang; C Cameron Yin; Joseph D Khoury; Wei Wang; Roberto N Miranda; Swaminathan Iyer; M James You; Jie Xu Journal: Cancers (Basel) Date: 2021-12-16 Impact factor: 6.639