• 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, and He Huang.
• From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of Hematology (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.) and the Department of Epidemiology and Statistics, School of Public Health (Y.Y.), Zhejiang University, and Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), Hangzhou, the Department of Medical Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou (B.L.), the Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing (Q.C.), Nanjing Bioheng Biotech, Nanjing (J.R.), and the Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, and Shanghai YaKe Biotechnology, Shanghai (A.H.C.) - all in China.
• N. Engl. J. Med. 2024 Apr 25; 390 (16): 146714801467-1480.

BackgroundPatients 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.MethodsWe 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.ResultsAfter 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).ConclusionsOur 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.).Copyright © 2024 Massachusetts Medical Society.

33 keywords...

hide…