序贯性CD19和CD22嵌合抗原受体T细胞（CAR-T）疗法在复发/难治性成人B细胞急性淋巴细胞白血病中的显著疗效和良好安全性。
Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia.
作者信息
Yang Tingting, Dong Yetian, Zhang Mingming, Feng Jingjing, Fu Shan, Xiao Pingnan, Hong Ruimin, Xu Huijun, Cui Jiazhen, Huang Simao, Wei Guoqing, Kong Delin, Geng Jia, Chang Alex H, Huang He, Hu Yongxian
机构信息
Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, China.
Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
出版信息
Exp Hematol Oncol. 2025 Jan 3;14(1):2. doi: 10.1186/s40164-024-00593-5.
BACKGROUND
Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited.
METHODS
This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS).
RESULTS
Twenty-three patients with a median age of 58.1 years (range 25.9-75.0) were enrolled. High-risk cytogenetic and genomic aberrations were identified in 43.5% of patients, and five patients had baseline extramedullary disease (EMD). The median interval between the two infusions was 3.8 months. Grade ≥ 3 hematological adverse events occurred at comparable rates after both infusions. Cytokine release syndrome was observed in 78.3% and 39.1% of patients after CD19 and CD22 CAR-T therapy, respectively. Two patients experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T. The median OS was not reached with a median follow-up of 19.4 months (range 8.7-45.6), while the median LFS was 20.8 months. OS and LFS rates were 91.3% and 67.1% at 1 year and 58.6% and 47.0% at 2 years, respectively. Eight patients experienced relapse, with the cumulative incidence of relapse being 28.6% at 1 year and 42.5% at 2 years. Higher baseline leukemia burden (≥ 64% bone marrow blasts) and the presence of EMD were significant risk factors for inferior OS and LFS, respectively.
CONCLUSIONS
Sequential CAR-T cell therapy demonstrated durable efficacy and a manageable safety profile in R/R B-ALL, providing a viable option to address antigen-loss relapse and improve long-term outcomes in high-risk adult patients.
背景
序贯性CD19和CD22嵌合抗原受体（CAR）-T细胞疗法为复发/难治性（R/R）B细胞急性淋巴细胞白血病（B-ALL）中抗原丢失导致的复发提供了一种有前景的方法；然而，成人患者中的研究仍然有限。
方法
本研究旨在评估2020年11月至2023年11月期间序贯性CD19和CD22 CAR-T细胞疗法在成年R/R B-ALL患者中的疗效和安全性（中国临床试验注册中心注册号：ChiCTR2100053871）。主要终点包括不良事件发生率、总生存期（OS）和无白血病生存期（LFS）。
结果
纳入了23例患者，中位年龄为58.1岁（范围25.9 - 75.0岁）。43.5%的患者存在高危细胞遗传学和基因组异常，5例患者有基线髓外疾病（EMD）。两次输注之间的中位间隔时间为3.8个月。两次输注后≥3级血液学不良事件的发生率相当。CD19和CD22 CAR-T治疗后，分别有78.3%和39.1%的患者发生细胞因子释放综合征。2例患者在CD19 CAR-T治疗期间发生2级免疫效应细胞相关神经毒性综合征（ICANS），CD22 CAR-T治疗期间未报告ICANS。中位随访19.4个月（范围8.7 - 45.6个月）时，未达到中位OS，而中位LFS为20.8个月。1年时OS和LFS率分别为91.3%和67.1%，2年时分别为58.6%和47.0%。8例患者复发，1年和2年时累积复发率分别为28.6%和42.5%。较高的基线白血病负担（≥64%骨髓原始细胞）和EMD的存在分别是OS和LFS较差的显著危险因素。
结论
序贯性CAR-T细胞疗法在R/R B-ALL中显示出持久的疗效和可控的安全性，为解决抗原丢失复发和改善高危成年患者的长期结局提供了一个可行的选择。
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