抗 CD19 嵌合抗原受体修饰 T 细胞疗法桥接异基因造血干细胞移植治疗复发/难治性 B 细胞急性淋巴细胞白血病:一项开放标签实用临床试验。

Anti-CD19 chimeric antigen receptor-modified T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia: An open-label pragmatic clinical trial.

机构信息

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.

出版信息

Am J Hematol. 2019 Oct;94(10):1113-1122. doi: 10.1002/ajh.25582. Epub 2019 Aug 2.

Abstract

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

摘要

嵌合抗原受体修饰的 T 细胞(CAR-T)疗法对复发/难治性 B 细胞急性淋巴细胞白血病(r/r B-ALL)患者有效且安全,但在无白血病生存方面的疗效有限。迫切需要新的策略来帮助 CAR-T 疗法实现持久的疗效。这项非随机干预性实用临床试验有一个特定的目的。它探索了巩固性异基因造血干细胞移植(allo-HSCT)是否可以改善 CAR-T 治疗后微小残留病阴性完全缓解(MRD CR)患者的长期预后。在第一阶段,58 例 r/r B-ALL 患者在淋巴耗竭化疗后接受 CAR-T 细胞的分剂量给药,其中 51 例(87.9%)达到 CR。在第二阶段,21/47 例无既往 allo-HSCT 且无禁忌证或其他限制的 MRD CR 患者在 CAR-T 治疗后 3 个月内自行接受巩固性 allo-HSCT。接受 allo-HSCT 的 MRD CR 患者与未接受 allo-HSCT 的患者的总生存(OS)无差异。然而,allo-HSCT 使无事件生存(EFS)和无复发生存(RFS)在亚组中显著延长。这在接受高(≥5%)输注前骨髓流式细胞术微小残留病(BM-FCM-MRD)评估或不良预后标志物(P < .05)的患者中更为明显。然而,在输注前 BM-FCM-MRD <5%且无不良预后标志物的患者中,EFS 和 RFS 无差异(P > .05)。总之,CAR-T 治疗桥接 allo-HSCT 是 r/r B-ALL 患者的一种安全有效的治疗策略,可延长 EFS 和 RFS,特别是在患者具有高输注前 BM-FCM-MRD 或不良预后标志物时。

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