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Donor-derived anti-CD19 CAR T cells compared with donor lymphocyte infusion for recurrent B-ALL after allogeneic hematopoietic stem cell transplantation

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Abstract

The efficacy and safety of donor-derived anti-CD19 CAR T cells vs DLI for the management of relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allo-hematopoietic stem cell transplantation (HSCT) remain unclear. Thirteen B-ALL patients with relapsed after allo-HSCT and thus were treated with donor-derived anti-CD19 CAR T-cell (study group). Fifteen B-ALL patients relapsed after allo-HSCT and thus were treated with DLI (DLI group). The rates of MRD-negative complete remission (61.5%) in the study group were significantly higher than those in the DLI group (13.3%) (p = 0.02). The complete remission duration in study group and DLI group were median 8.0 months (range, 3–25 months) and 4.4 months (range, 1–25 months; p = 0.026), respectively. The overall survival of patients in the study group was superior to that of the DLI group: 9.5 months (range,3–25 months) versus 5.5 months (range, 1–25 months; p = 0.030). One patient with grade 1 acute graft-versus-host disease (aGVHD) was identified in the study group. While five (33.3%) patients in the DLI group developed grades III–IV aGVHD. Three patients (23.07%) developed grade 3 or 4 cytokine release syndrome in the study group. This study suggested that donor-derived anti-CD19 CAR T-cell therapy is promising, safe, and potentially effective for relapsed B-ALL after allo-HSCT and may be superior to DLI.

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Fig. 1: Patient survival and efficacy assessment of CAR T-cell and DLI treatment.
Fig. 2: Dynamic changes of Patient 6 who was diagnosed with HLH within 30 days after infusion of anti-CD19 CAR T cells.

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Acknowledgements

We would like to thank to all members of the study team, the patients and their families, and Uni CAR Technology Co., Ltd, Shanghai, China.

Funding

This work was jointly supported by the National Natural Science Foundation of Jiangsu Province [SBE2018740700], the Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Key Medical Center (YXZXA2016002), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. These authors contributed equally: **gsheng Hua, Jian Zhang, **nyou zhang

  2. These authors jointly supervised this work: **aowen Tang, Depei Wu, Huiying Qiu

Authors and Affiliations

  1. Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, P.R. China

    **gsheng Hua, Jian Zhang, **aoxia Wu, Lili Zhou, **ebing Bao, Yue Han, Miao Miao, Caixia Li, Chengcheng Fu, Suning Chen, **aowen Tang, Depei Wu & Huiying Qiu

  2. Department of Hematology, Taizhou Municipal Hospital, Taizhou, Zhejiang, 318000, China

    **gsheng Hua

  3. Department of Hematology, Shenzhen People’s Hospital, Second Clinical Medical College of **an University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China

    **nyou zhang

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  1. **gsheng Hua
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Contributions

JZ, HQ, XT, and DW contributed to the conception and design of the study. YH, MM, CL, and CF provided clinical patients. JH, JZ, XW, and LZ collected and analyzed the clinical data. JH and JZ wrote the manuscript. Xz, JZ, Sc, and HQ provided writing advice. Xz, JZ, and HQ revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to **aowen Tang, Depei Wu or Huiying Qiu.

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The authors declare that they have no conflict of interest.

Ethics

This study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University (IRB ID:2015070). The patients and donors provided their written informed consent according to the Declaration of Helsinki. The study was registered at https://www.clinicalTrials.gov as NCT03275493.

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Hua, J., Zhang, J., zhang, X. et al. Donor-derived anti-CD19 CAR T cells compared with donor lymphocyte infusion for recurrent B-ALL after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 1056–1064 (2021). https://doi.org/10.1038/s41409-020-01140-6

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