Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis

Authors:
  • YHYongxian Hu
    Yongxian Hu
  • MZMingming Zhang
    Mingming Zhang
  • TYTingting Yang
    Tingting Yang
  • ZMZhuomao Mo
    Zhuomao Mo
  • GWGuoqing Wei
    Guoqing Wei
  • RJRuirui Jing
    Ruirui Jing
  • HZHouli Zhao
    Houli Zhao
  • RCRongrong Chen
    Rongrong Chen
  • TGTianning Gu
    Tianning Gu
  • PXPingnan Xiao
    Pingnan Xiao
  • RHRuimin Hong
    Ruimin Hong
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Abstract
Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).
Funding Information
  • Key Project of Science and Technology Department of Zhejiang Province (2021C03010, 2023C03060)
  • National Natural Science Foundation of China (82130003, 82270234, 82271874)

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