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Lookup NU author(s): Sam SeeryORCiD
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© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.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(s): Pan J, Tan Y, Shan L, Seery S, Deng B, Ling Z, Xu J, Duan J, Wang Z, Wang K, Yu X, Zheng Q, Xu X, Hu G, Tan T, Yuan Y, Tian Z, Yan F, Han Y, Zhang J, Feng X
Publication type: Article
Publication status: Published
Journal: Nature Medicine
Year: 2024
Volume: 31
Pages: 126–136
Print publication date: 01/01/2025
Online publication date: 01/10/2024
Acceptance date: 20/08/2024
ISSN (print): 1078-8956
ISSN (electronic): 1546-170X
Publisher: Nature Research
URL: https://doi.org/10.1038/s41591-024-03282-2
DOI: 10.1038/s41591-024-03282-2
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