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

Yi Luo; Lei Gao; Jia Liu; Luxin Yang; Lu Wang; Xiaoyu Lai; Shichun Gao; Lizhen Liu; Lu Zhao; Yishan Ye; Manning Wang; Lianjun Shen; W William Cao; Dongrui Wang; Wenling Li; Xi Zhang; He Huang

doi:10.1016/j.eclinm.2023.102377

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

Authors

Yi Luo^{1

2

3

4}, Lei Gao⁵, Jia Liu⁶, Luxin Yang^{1

2

3

4}, Lu Wang⁵, Xiaoyu Lai^{1

2

3

4}, Shichun Gao⁵, Lizhen Liu^{1

2

3

4}, Lu Zhao⁵, Yishan Ye^{1

2

3

4}, Manning Wang⁶, Lianjun Shen⁶, W William Cao⁶, Dongrui Wang^{1

2

3

4}, Wenling Li⁶, Xi Zhang⁵, He Huang^{1

2

3

4}

Affiliations

¹ The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
² Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
³ Institute of Hematology, Zhejiang University, Hangzhou, China.
⁴ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China.
⁵ Medical Center of Hematology, Xinqiao Hospital, Chongqing, China.
⁶ Gracell Biotechnologies Ind., Shanghai, China.

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 × 10⁵/kg (n = 3) or 2 × 10⁶/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_max 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.

Keywords: Allogeneic hematopoietic stem cell transplantation; B-cell acute lymphoblastic leukemia; Donor-derived CAR T; Safety.

Associated data

ClinicalTrials.gov/NCT04516551