CAR19/22 T cell cocktail therapy for B-ALL relapsed after allogeneic hematopoietic stem cell transplantation.

Abstract

B cell acute lymphocytic leukemia (B-ALL) patients who have relapsed after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, and there is currently no standard approach available. Chimeric antigen receptor (CAR)-T cells induce high rates of initial response and long-term remission among patients with B-cell malignancies, especially B-ALL. Meanwhile, sequential infusion of CAR19/22 T cells has been proven to be effective at preventing tumor immune escape. In the present study, we retrospectively analyzed 23 B-ALL patients who relapsed after allogeneic (allo)-HSCT and underwent sequential infusion of CAR19/22 T cells, including nine donor-derived and 14 recipient-derived, in our center from July 2016 to July 2020, to evaluate the safety and efficacy of the cocktail of two single-specific CAR-T cells in B-ALL patients relapsed after transplantation. Except for one patient refusing evaluation, the remaining 22 patients achieved minimal residual disease (MRD)-negative complete remission within 30 days after CAR-T infusion. Most toxicities were slight and reversible. The estimated 12-month progression-free survival (PFS) rate was 59.2% (95% confidence interval [CI], 35.9% to 76.5%), and the estimated 12-month overall survival (OS) rate was 67.4% (95% CI, 43.2% to 83.1%). Only two patients had CD19-negative recurrence. In addition, early recurrence after transplantation, graft-versus-host disease (GVHD) and severe infection after CAR-T infusion were poor prognostic factors. Our results indicate that sequential infusion of CAR19/22 T cells is safe and effective for relapsed ALL patients after HSCT. This trial was registered at www.chictr.org.cn as #ChiCTR-OPN-16008526.

• Authors: Nan Yan, Na Wang, Gaoxiang Wang, Liang Huang, Chunrui Li, Di Wang, Jue Wang, Lifang Huang, Fankai Meng, Jia Wei, Liting Chen, Xia Mao, Jianfeng Zhou, Yicheng Zhang, Yang Cao
• Journal: Cytotherapy (Cytotherapy) Vol. 24 Issue 8 Pg. 841-849 (08 2022) ISSN: 1477-2566 [Electronic] England
• PMID: 35256277 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD19
• Receptors, Chimeric Antigen

Topics

• Acute Disease
• Antigens, CD19
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Immunotherapy, Adoptive (methods)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (therapy)
• Receptors, Chimeric Antigen
• Retrospective Studies
• T-Lymphocytes