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

in The New England journal of medicine by Yongxian Hu, Mingming Zhang, Tingting Yang, Zhuomao Mo, Guoqing Wei, Ruirui Jing, Houli Zhao, Rongrong Chen, Cheng Zu, Tianning Gu, Pingnan Xiao, Ruimin Hong, Jingjing Feng, Shan Fu, Delin Kong, Huijun Xu, Jiazhen Cui, Simao Huang, Bin Liang, Xiaolin Yuan, Qu Cui, Hongshan Guo, Yunxian Yu, Youqin Feng, Chunxiang Jin, Jiangtao Ren, Alex H Chang, Dongrui Wang, He Huang

TLDR

  • This study tested a new way to treat patients with a type of cancer called relapsed or refractory hematologic cancers. The treatment involved using a special type of cell called CAR T-cells to fight the cancer, followed by a procedure called haploidentical HSCT. The study found that this approach was safe and effective, with most patients achieving complete remission and some experiencing serious but reversible side effects. The estimated 1-year overall survival was 68% and the estimated 1-year disease-free survival was 54%.

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.).

Overview

  • The study tested a novel strategy of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. The primary objective was to evaluate the safety and efficacy of this approach in achieving complete remission and minimizing toxic effects. The study was funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province, and registered on ClinicalTrials.gov with numbers NCT04599556 and NCT04538599.

Comparative Analysis & Findings

  • After CAR T-cell therapy led to complete remission with incomplete hematologic recovery and grade 4 pancytopenia, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. One patient died on day 13 of septic shock and encephalitis, while eight patients had full donor chimerism and one 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, two had a relapse of CD7-negative leukemia, and one 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). The study suggests 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.

Implications and Future Directions

  • The study's findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is a safe and effective approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. However, the study had limitations, such as a small sample size and the need for further research to validate the results. Future studies could explore the use of different CAR T-cell therapies and HSCT regimens, as well as the potential for personalized medicine approaches. The study highlights the importance of continued research in the field of CAR T-cell therapy and allogeneic HSCT for the treatment of relapsed or refractory hematologic cancers.
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