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
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
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抗 CD19 嵌合抗原受体修饰 T 细胞疗法桥接同种异体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
DOI：
10.1002/ajh.25582
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发表时间：
2019-08-02
影响因子：
12.8
通讯作者：
Hu, Yu
中科院分区：
文献类型：
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作者：
Jiang, Huiwen;Li, Chenggong;Hu, Yu
嵌合抗原受体修饰的T细胞(CAR-T)治疗复发/难治性B细胞急性淋巴细胞白血病(r/rB-ALL)是有效和安全的，但其长期无白血病生存的价值受到限制。迫切需要新的策略来帮助CAR-T疗法取得持久的效果。这项非随机干预性实用型临床试验有一个特别的目的。探讨巩固异基因造血干细胞移植(allo-HSCT)能否改善CAR-T治疗后微小残留病阴性完全缓解(MRD-CR)患者的远期预后。在第一阶段，58例B-ALL患者在淋巴清除化疗后接受了分次剂量的CAR-T细胞治疗，51例(87.9%)获得CR。在第二阶段，47例MRD-CR患者中有21例在接受CAR-T治疗后3个月内自愿接受了巩固的allo-HSCT。接受allo-HSCT的MRD-CR患者和未接受allo-HSCT的患者在总存活率(OS)方面没有差异。然而，在亚组中，allo-HSCT显著延长了无事件生存期(EFS)和无复发生存期(RFS)。这是通过流式细胞仪(BM-FCM-MRD)评估输注前骨髓MRD的高(>；=5%)或较差的预后标志物(P<；0.05)。然而，输注前BM-FCM-MRD患者的EFS和RFS没有差异(P>0.05)。综上所述，CAR-T治疗过渡到allo-HSCT对于r/r B-ALL患者是一种安全有效的治疗策略，并可能延长他们的EFS和RFS，特别是当他们输注前BM-FCM-MRD较高或预后标志物较差时。
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 .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.