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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

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Abstract

Objective

This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells (CAR-T cells) versus chemotherapy plus donor lymphocyte infusion (chemo-DLI) for treating relapsed CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods

Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed. Twenty-two patients were treated with CAR-T cells (CAR-T group), and 21 with chemotherapy plus DLI (chemo-DLI group). The complete remission (CR) and minimal residual disease (MRD)-negative CR rates, leukemia-free survival (LFS) rate, overall survival (OS) rate, and incidence of acute graft-versus-host disease (aGVHD), cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were compared between the two groups.

Results

The CR and MRD-negative CR rates in the CAR-T group (77.3% and 61.5%) were significantly higher than those in the chemo-DLI group (38.1% and 23.8%) (P=0.008 and P=0.003). The 1- and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group: 54.5% and 50.0% vs. 9.5% and 4.8% (P=0.0001 and P=0.00004). The 1- and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1% and 54.5% vs. 19% and 9.5% (P=0.011 and P=0.003). Six patients (28.6%) with grade 2–4 aGVHD were identified in the chemo-DLI group. Two patients (9.1%) in the CAR-T group developed grade 1–2 aGVHD. Nineteen patients (86.4%) developed CRS in the CAR-T group, comprising grade 1–2 CRS in 13 patients (59.1%) and grade 3 CRS in 6 patients (27.3%). Two patients (9.1%) developed grade 1–2 ICANS.

Conclusion

Donor-derived anti-CD19 CAR-T-cell therapy may be better, safer, and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Xu Tan, Yan Shen & Shi-feng Lou

  2. Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burns and Cobmined Injury, Army Medical University, Chongqing, 400037, China

    Xu Tan, Xiao-qi Wang, Cheng Zhang, Xian-lan Zhao, Han Yao, Guo Chen, Ying-ying Ma, Qin Wen, Lei Gao, Li Gao, Pei-yan Kong & Xi Zhang

  3. Jinfeng Laboratory, Chongqing, 401329, China

    Xi Zhang

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  1. Xu Tan
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  2. Xiao-qi Wang
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Corresponding authors

Correspondence to Xi Zhang or Shi-feng Lou.

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The authors declare that they have no conflict of interests.

Additional information

This work was supported by grants from the National Natural Science Foundation of China (No. 82020108004), the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University (No. 2018JSLC0020), Chongqing Science and Technology Innovation Leading Talent (No. CSTCCXLJRC201718), and Natural Science Foundation of Chongqing Innovation Group Science Program (No. cstc2021jcyj-cxttX0001).

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Tan, X., Wang, Xq., Zhang, C. et al. 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 43, 733–740 (2023). https://doi.org/10.1007/s11596-023-2746-1

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  • DOI: https://doi.org/10.1007/s11596-023-2746-1

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