Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia

Tingting Yang^#^{1

2

3}, Yetian Dong^#^{1

2

3}, Mingming Zhang^{1

2

3}, Jingjing Feng^{1

2

3}, Shan Fu^{1

2

3}, Pingnan Xiao^{1

2

3}, Ruimin Hong^{1

2

3}, Huijun Xu^{1

2

3}, Jiazhen Cui^{1

2

3}, Simao Huang^{1

2

3}, Guoqing Wei^{1

2

3}, Delin Kong^{1

2

3}, Jia Geng⁴, Alex H Chang^{5

6}, He Huang^{7

8

9}, Yongxian Hu^{10

11

12}

Affiliations

¹ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China.
² Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
³ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China.
⁴ Department of Radiology of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁵ Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China. changah@yakebiotech.com.
⁶ Shanghai YaKe Biotechnology Ltd., Shanghai, China. changah@yakebiotech.com.
⁷ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China. huanghe@zju.edu.cn.
⁸ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China. huanghe@zju.edu.cn.
⁹ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China. huanghe@zju.edu.cn.
¹⁰ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China. 1313016@zju.edu.cn.
¹¹ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China. 1313016@zju.edu.cn.
¹² Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China. 1313016@zju.edu.cn.

^# Contributed equally.

PMID: 39754190
PMCID: PMC11697943
DOI: 10.1186/s40164-024-00593-5

Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia

Tingting Yang et al. Exp Hematol Oncol. 2025.

. 2025 Jan 3;14(1):2.

doi: 10.1186/s40164-024-00593-5.

Authors

Affiliations

¹ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China.
² Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
³ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China.
⁴ Department of Radiology of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁵ Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China. changah@yakebiotech.com.
⁶ Shanghai YaKe Biotechnology Ltd., Shanghai, China. changah@yakebiotech.com.
⁷ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China. huanghe@zju.edu.cn.
⁸ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China. huanghe@zju.edu.cn.
⁹ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China. huanghe@zju.edu.cn.
¹⁰ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China. 1313016@zju.edu.cn.
¹¹ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China. 1313016@zju.edu.cn.
¹² Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China. 1313016@zju.edu.cn.

^# Contributed equally.

PMID: 39754190
PMCID: PMC11697943
DOI: 10.1186/s40164-024-00593-5

Abstract

Background: Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited.

Methods: This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS).

Results: Twenty-three patients with a median age of 58.1 years (range 25.9-75.0) were enrolled. High-risk cytogenetic and genomic aberrations were identified in 43.5% of patients, and five patients had baseline extramedullary disease (EMD). The median interval between the two infusions was 3.8 months. Grade ≥ 3 hematological adverse events occurred at comparable rates after both infusions. Cytokine release syndrome was observed in 78.3% and 39.1% of patients after CD19 and CD22 CAR-T therapy, respectively. Two patients experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T. The median OS was not reached with a median follow-up of 19.4 months (range 8.7-45.6), while the median LFS was 20.8 months. OS and LFS rates were 91.3% and 67.1% at 1 year and 58.6% and 47.0% at 2 years, respectively. Eight patients experienced relapse, with the cumulative incidence of relapse being 28.6% at 1 year and 42.5% at 2 years. Higher baseline leukemia burden (≥ 64% bone marrow blasts) and the presence of EMD were significant risk factors for inferior OS and LFS, respectively.

Conclusions: Sequential CAR-T cell therapy demonstrated durable efficacy and a manageable safety profile in R/R B-ALL, providing a viable option to address antigen-loss relapse and improve long-term outcomes in high-risk adult patients.

Keywords: Chimeric antigen receptor; Relapsed/refractory B-cell acute lymphoblastic leukemia; Sequential therapy.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study involved human participants and was approved by the Ethics Review Committee of the First Affiliated Hospital of Zhejiang University. Informed consent was obtained from all participants before participation. Consent for publication: Informed consent was obtained from patients. Competing interests: The authors declare no competing interests.

Figures

**Fig. 1**
Diagram of the sequential treatment procedure

**Fig. 2**
Clinical outcomes. A Swimmer plot showing the duration of response and survival outcomes post-infusion for all treated patients (n = 23). CR/CRi, complete remission/complete remission with incomplete hematologic recovery; MRD⁻, minimal residual disease-negative. B, C Kaplan–Meier estimates of overall survival (OS, B) and leukemia-free survival (LFS, C) in all patients. D, E Kaplan–Meier estimates of OS (D) and LFS (E) in patients without extramedullary disease (EMD) (n = 18) versus those with EMD (n = 5). F Cumulative incidence of relapse in all patients. G Cumulative incidence of relapse in patients without EMD versus those with EMD

**Fig. 3**
Dynamics of CAR-T cell expansion and comparison of peak CAR-T levels. A Expansion of CAR-T cells over time post-infusion in all patients. B CAR-T cell expansion between autologous and donor-derived CAR-T cells. C Peak CAR-T cell levels and the number of days to reach peak expansion. D Peak CD19 CAR-T cell levels (top) and peak CD22 CAR-T cell levels (bottom) between patients with ongoing remission and those who relapsed. E Peak CD19 CAR-T cell levels (top) and peak CD22 CAR-T cell levels (bottom) between autologous and donor-derived CAR-T cells

See this image and copyright information in PMC

References

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Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia

Affiliations

Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources