Luo Yi, Gao Lei, Liu Jia, Yang Luxin, Wang Lu, Lai Xiaoyu, Gao Shichun, Liu Lizhen, Zhao Lu, Ye Yishan, Wang Manning, Shen Lianjun, Cao W William, Wang Dongrui, Li Wenling, Zhang Xi, Huang He
The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
EClinicalMedicine. 2023 Dec 21;67:102377. doi: 10.1016/j.eclinm.2023.102377. eCollection 2024 Jan.
BACKGROUND: Although chimeric antigen receptor-modified T cells (CAR T) cell therapy has been widely reported in improving the outcomes of B-cell acute lymphoblastic leukemia (B-ALL), less research about the feasibility and safety of donor-derived CAR T after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was reported. METHODS: This phase 1 clinical trial aims to evaluate safety and efficacy of donor-derived anti-CD19 CAR T cells (GC007g) in B-ALL patients who relapsed after allo-HSCT. This trial is registered with ClinicalTrials.gov, NCT04516551. FINDINGS: Between 15 March 2021 and 19 May 2022, fifteen patients were screened, three patients were excluded due to withdraw of consent, donor's reason, and death, respectively. Patients received donor-derived CAR T cells infusions at 6 × 10/kg (n = 3) or 2 × 10/kg (n = 6) dose level. The median time from HSCT to relapse was 185 days (range, 81-2063). The median age of patients was 31 years (range 21-48). Seven patients (77.8%) had BCR-ABL fusion gene. CAR T cells expanded in vivo and the median time to reach C was 9 days (range, 7-11). One patient had hyperbilirubinemia after GC007g infusion which was defined as a dose-limiting toxicity. All patients experienced CRS and hematological adverse events. Three patients had acute graft-versus-host-disease (grade I, n = 1; grade II, n = 1; grade IV, n = 1) and all resolved after treatment. They received CAR T cells from matched sister, haploidentical matched father and sisiter, respectively. At 28 days after infusion, all patients achieved complete remission with/without incomplete hematologic recovery (CRi/CR) with undetectable MRD. At a median follow-up of 475 days (range 322-732), seven patients remained in CR/CRi while two had CD19-negative relapse. The overall response rates (ORR) were 100% (9/9), 88.9% (8/9), and 75% (6/8) at 3 month, 6 month, and 12 month, respectively. The 1-year progression-free and overall survival were 77.8% and 85.7%, respectively. INTERPRETATION: GC007g expanded and induced durable remission in patients with B-ALL relapsed after allo-HSCT, with manageable safety profiles. FUNDING: Gracell Biotechnologies Inc.
J Hematol Oncol. 2025-8-29
Eur J Epidemiol. 2025-2
Immunotherapy. 2024
J Clin Oncol. 2021-5-20