Sixteen patients with r/r T-ALL, including previous recipients of anti-CD7 CAR T cell therapy and/or allogeneic stem cell transplant, were treated with allogeneic, CD5-disrupted anti-CD5 CAR-T. The starting dose of 1e6 cells/kg achieved a 100% ORR, and was not further escalated. The majority of patients experienced cytopenia, low-grade CRS, and mild GvHD symptoms (rashes). A high rate of severe and fatal infections was associated with persistent cytopenia, mainly in patients who did not receive subsequent stem cell transplant. CAR T cells were detected in blood, CSF, and GvHD lesions, and CD5+ lymphocytes were depleted in blood after treatment.
Contributed by Alex Najibi
ABSTRACT: Refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL) patients have poor prognoses, due to the lack of effective salvage therapies. Recently, CD7-targeting chimeric antigen receptor (CAR)-T therapies show efficacy in patients with r/r T-ALL, but relapse with CD7 loss is common. This study evaluates a CD5-gene-edited CAR-T cell therapy targeting CD5 in 19 r/r T-ALL patients, most of whom had previously failed CD7 CAR-T interventions. CAR-T products were derived from previous transplant donors (Cohort A) or newly matched donors (Cohort B). Primary endpoints were dose-limiting toxicity at 21 days and adverse events within 30 days. Secondary endpoints were responses, pharmacokinetics and severe adverse events after 30 days. A total of 16 received infusions, 10 at target dose of 1 × 106 kg-1. All encountered grade 3-4 cytopenias and one had a grade 3 infection within 30 days. All patients (100%) achieved complete remission or complete remission with incomplete blood count recovery by day 30. At a median follow-up of 14.3 months, four received transplantation; three were in remission and one died of infection. Of 12 untransplanted patients, 2 were in remission, 3 relapsed, 5 died of infection and 2 of thrombotic microangiopathy. CAR-T cells persisted and cleared CD5+ T cells. CD5- T cells, mostly CD5-gene-edited, increased but remained below normal levels. These results suggest this CD5-specific CAR-T intervention has a high remission rate for T-ALL patients. Evidence also suggests the risk of late-onset severe infection may be mitigated with consolidative transplantation. This study provides insights that could help to optimize this promising intervention. ClinicalTrials.gov registration: NCT05032599.
Author Info: (1) State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. panj@gobroadheal
Author Info: (1) State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. panj@gobroadhealthcare.com. (2) State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. Tianjin Institutes of Health Science, Tianjin, China. (3) State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. Tianjin Institutes of Health Science, Tianjin, China. (4) School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. (5) Cytology Laboratory, Beijing Gobroad Boren Hospital, Beijing, China. (6) State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. (7) State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. (8) State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. (9) State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. (10) State Key Laboratory of Experimental Hematology, Boren Clinical Translational Center, Department of Hematology, Beijing Gobroad Boren Hospital, Beijing, China. (11) Medical Laboratory, Beijing Gobroad Boren Hospital, Beijing, China. (12) Medical Laboratory, Beijing Gobroad Boren Hospital, Beijing, China. (13) Medical Laboratory, Beijing Gobroad Boren Hospital, Beijing, China. (14) Nanjing IASO Biotherapeutics, Nanjing, China. (15) Nanjing IASO Biotherapeutics, Nanjing, China. (16) Department of Biostatistics, University of Texas MD Anderson Cancer Center, Austin, TX, USA. (17) Gobroad Research Center, Gobroad Medical Group, Beijing, China. (18) Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China. (19) State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. Tianjin Institutes of Health Science, Tianjin, China. (20) Department of Hospital Management, Gobroad Medical Group, Beijing, China. (21) State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. fengxiaoming@ihcams.ac.cn. Tianjin Institutes of Health Science, Tianjin, China. fengxiaoming@ihcams.ac.cn. Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China. fengxiaoming@ihcams.ac.cn.
