Wang Yu, Xue Yu-Juan, Zuo Ying-Xi, Jia Yue-Ping, Lu Ai-Dong, Zeng Hui-Min, Zhang Le-Ping
Department of Pediatrics, Peking University People's Hospital, Peking University, Beijing, China.
Cancer Res Treat. 2024 Jul;56(3):945-955. doi: 10.4143/crt.2023.1205. Epub 2024 Feb 13.
Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients.
Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients.
All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not.
CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.
化疗一直是B细胞急性淋巴细胞白血病（B-ALL）患者的主要治疗方法。然而，仍有一些患者对化疗不敏感，包括难治性/复发性（R/R）疾病患者和微小残留病（MRD）复发患者。嵌合抗原受体T淋巴细胞（CAR-T）疗法可能为这些患者提供一种新的治疗选择。
我们机构开展了一项单臂前瞻性临床试验（ChiCTR-OPN-17013507），使用CAR-T-19治疗R/R B-ALL和MRD复发患者。共纳入115例年龄在1至25岁（中位年龄8岁）的患者，其中包括67例R/R患者和48例MRD复发的CD19阳性B-ALL患者。
所有患者均实现形态学完全缓解（CR），输注后1个月内，115例患者中有111例（96.5%）实现MRD阴性CR。中位随访时间为48.4个月，估计4年无白血病生存率（LFS）和总生存率（OS）分别为68.7%±4.5%和70.7%±4.3%。输注前不同疾病状态的患者在长期疗效上无显著差异（4年OS：MRD复发 vs. R/R B-ALL，70.6%±6.6% vs. 66.5%±6.1%，p = 0.755；4年LFS：MRD复发 vs. R/R B-ALL，67.3%±7.0% vs. 63.8%±6.2%，p = 0.704）。CAR-T治疗后接受移植的R/R B-ALL患者的OS和LFS优于未接受移植的患者。然而，对于MRD复发患者，无论是否接受造血干细胞移植，OS和LFS均无显著差异。
CD19 CAR-T疗法有效且安全地治愈了R/R B-ALL和MRD复发患者。
