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

Tingting Yang; Yetian Dong; Mingming Zhang; Jingjing Feng; Shan Fu; Pingnan Xiao; Ruimin Hong; Huijun Xu; Jiazhen Cui; Simao Huang; Guoqing Wei; Delin Kong; Jia Geng; Alex H Chang; He Huang; Yongxian Hu

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

Exp Hematol Oncol. 2025 Jan 3;14(1):2. doi: 10.1186/s40164-024-00593-5.

Authors

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. [email protected].
⁶ Shanghai YaKe Biotechnology Ltd., Shanghai, China. [email protected].
⁷ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China. [email protected].
⁸ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China. [email protected].
⁹ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China. [email protected].
¹⁰ Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China. [email protected].
¹¹ Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China. [email protected].
¹² Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, Zhejiang, China. [email protected].

^# Contributed equally.

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.

Abstract

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