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Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or refractory B-cell acute lymphoblastic leukemia after allogeneic HSCT: a phase 1 trial.

作者信息

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

机构信息

The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.

出版信息

EClinicalMedicine. 2023 Dec 21;67:102377. doi: 10.1016/j.eclinm.2023.102377. eCollection 2024 Jan.


DOI:10.1016/j.eclinm.2023.102377
PMID:38204488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10776428/
Abstract

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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/bb77d302f344/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/2bc223ba5eef/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/36ff6eaf43d6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/e12c0ad69c0c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/bb77d302f344/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/2bc223ba5eef/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/36ff6eaf43d6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/e12c0ad69c0c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/242d/10776428/bb77d302f344/figs1.jpg

相似文献

[1]
Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or refractory B-cell acute lymphoblastic leukemia after allogeneic HSCT: a phase 1 trial.

EClinicalMedicine. 2023-12-21

[2]
Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy.

Front Immunol. 2021

[3]
[Allogeneic donor-derived CD19 CAR-T therapy of relapsed B-cell acute lmphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2021-5-14

[4]
[Maintenance therapy following CD19 CAR-T treatment for relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2020-6-14

[5]
Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia.

Front Immunol. 2021

[6]
Donor-derived CD19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD19-positive B-ALL After Allogeneic Hematopoietic Stem Cell Transplantation.

Curr Med Sci. 2023-8

[7]
Allogeneic Donor-Derived Anti-CD19 CAR T Cell Is a Promising Therapy for Relapsed/Refractory B-ALL After Allogeneic Hematopoietic Stem-Cell Transplantation.

Clin Lymphoma Myeloma Leuk. 2020-9

[8]
[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2024-1-14

[9]
[Efficacy of CD19 Chimeric Antigen Receptors T Cells in the Treatment of Relapsed Patients with B Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019-8

[10]
Case report: Two pediatric cases of long-term leukemia-free survival with relapsed acute T-lymphoblastic leukemia treated with donor CD7 CAR-T cells bridging to haploidentical stem cell transplantation.

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引用本文的文献

[1]
Recent advances in universal chimeric antigen receptor T cell therapy.

J Hematol Oncol. 2025-8-29

[2]
Case Report: CD19 CAR-T cells derived from recipient of umbilical cord blood transplantation effectively treated relapsed acute lymphoblastic leukemia after UCBT.

Front Immunol. 2025-5-19

[3]
Association between maternal cancer and the incidence of cancer in offspring.

Eur J Epidemiol. 2025-2

[4]
Engineering a controllable and reversible switch for CAR-based cellular immunotherapies via a genetic code expansion system.

J Hematol Oncol. 2024-12-18

[5]
GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation - successfully treated by extracorporeal photopheresis.

Front Immunol. 2024-11-18

[6]
Long-term survival with donor CD19 CAR-T cell treatment for relapsed patients after allogeneic hematopietic stem cell transplantation.

J Hematol Oncol. 2024-10-29

[7]
Allogeneic CAR-T cells for cancer immunotherapy.

Immunotherapy. 2024

[8]
Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment.

Bioact Mater. 2024-9-10

[9]
Extracorporeal photopheresis as a promising strategy for the treatment of graft-versus-host disease after CAR T-cell therapy.

Blood Adv. 2024-6-11

本文引用的文献

[1]
Allogeneic, donor-derived, second-generation, CD19-directed CAR-T cells for the treatment of pediatric relapsed/refractory BCP-ALL.

Blood. 2023-7-13

[2]
Safety and efficacy of autologous and allogeneic humanized CD19-targeted CAR-T cell therapy for patients with relapsed/refractory B-ALL.

J Immunother Cancer. 2023-2

[3]
CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany.

Blood Adv. 2023-6-13

[4]
Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells.

Blood Adv. 2023-2-28

[5]
Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse.

Front Oncol. 2021-11-1

[6]
Graft-versus-host disease risk after chimeric antigen receptor T-cell therapy: the diametric opposition of T cells.

Br J Haematol. 2021-12

[7]
[CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi. 2021-4-14

[8]
Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL.

J Clin Oncol. 2021-5-20

[9]
Combination of CD19 and CD22 CAR-T cell therapy in relapsed B-cell acute lymphoblastic leukemia after allogeneic transplantation.

Am J Hematol. 2021-6-1

[10]
Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia.

Blood. 2021-4-8

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