CD19 嵌合抗原受体 T 细胞治疗后复发的儿童 B 细胞急性淋巴细胞白血病中 CD19 和 CD22 嵌合抗原受体 T 细胞联合给药的安全性和有效性。
Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy.
机构信息
Department of Hematology/Oncology, Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Hematology/Oncology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
出版信息
J Transl Med. 2023 Mar 22;21(1):213. doi: 10.1186/s12967-023-04019-4.
BACKGROUND
CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed or refractory pediatric B-lineage acute lymphoblastic leukemia (B-ALL). However, poor results are obtained when the same product is reused in patients who relapse after CAR-T. Therefore, there is a need to explore the safety and efficacy of co-administration of CD19- and CD22-targeted CAR-T as a salvage second CAR-T therapy (CART2) in B-ALL patients who relapse after their first CD19 CAR-T treatment (CART1).
METHODS
In this study, we recruited five patients who relapsed after CD19-targeted CAR-T. CD19- and CD22-CAR lentivirus-transfected T cells were cultured separately and mixed before infusion in an approximate ratio of 1:1. The total dose range of CD19 and CD22 CAR-T was 4.3 × 10-1.5 × 10/kg. Throughout the trial, we evaluated the patients' clinical responses, side effects, and the expansion and persistence of CAR-T cells.
RESULTS
After CART2, all five patients had minimal residual disease (MRD)-negative complete remission (CR). The 6- and 12-month overall survival (OS) rates were 100%. The median follow-up time was 26.3 months. Three of the five patients bridged to consolidated allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CART2 and remained in MRD-negative CR at the cut-off time. In patient No. 3 (pt03), CAR-T cells were still detected in the peripheral blood (PB) at 347 days post-CART2. Cytokine release syndrome (CRS) only occurred with a grade of ≤ 2, and no patients experienced symptoms of neurologic toxicity during CART2.
CONCLUSIONS
Mixed infusion of CD19- and CD22-targeted CAR-T cells is a safe and effective regimen for children with B-ALL who relapse after prior CD19-targeted CAR-T therapy. Salvage CART2 provides an opportunity for bridging to transplantation and long-term survival.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2000032211. Retrospectively registered: April 23, 2020.
背景
嵌合抗原受体 T 细胞（CAR-T）疗法靶向 CD19 在治疗复发/难治性儿童 B 细胞急性淋巴细胞白血病（B-ALL）方面显示出显著疗效。然而，当同一产品在 CAR-T 后复发的患者中重复使用时，结果不佳。因此，有必要探讨在接受首次 CD19 CAR-T 治疗（CART1）后复发的 B-ALL 患者中联合使用 CD19 和 CD22 靶向 CAR-T 作为挽救性第二 CAR-T 治疗（CART2）的安全性和有效性。
方法
本研究招募了 5 例 CD19 靶向 CAR-T 后复发的患者。将 CD19- 和 CD22-CAR 慢病毒转染的 T 细胞分别培养，在输注前按大约 1:1 的比例混合。CD19 和 CD22 CAR-T 的总剂量范围为 4.3×10-1.5×10/kg。在整个试验过程中，我们评估了患者的临床反应、副作用以及 CAR-T 细胞的扩增和持续时间。
结果
在接受 CART2 后，所有 5 例患者均达到微小残留病灶（MRD）阴性完全缓解（CR）。6 个月和 12 个月的总生存率（OS）分别为 100%。中位随访时间为 26.3 个月。在接受 CART2 后，5 例患者中的 3 例桥接巩固性异基因造血干细胞移植（allo-HSCT），并在截止时间仍处于 MRD 阴性 CR。在患者 3（pt03）中，在接受 CART2 后 347 天仍可在外周血（PB）中检测到 CAR-T 细胞。细胞因子释放综合征（CRS）仅发生在≤2 级，在 CART2 期间没有患者出现神经毒性症状。
结论
对于接受过 CD19 靶向 CAR-T 治疗后复发的 B-ALL 患儿，混合输注 CD19 和 CD22 靶向 CAR-T 细胞是一种安全有效的治疗方案。挽救性 CART2 为桥接移植和长期生存提供了机会。
试验注册
中国临床试验注册中心，ChiCTR2000032211。回顾性注册：2020 年 4 月 23 日。
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