Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia.

IF 9.4 1区医学 Q1 HEMATOLOGY

Experimental Hematology & Oncology Pub Date : 2025-01-03 DOI:10.1186/s40164-024-00593-5

Tingting Yang, Yetian Dong, Mingming Zhang, Jingjing Feng, Shan Fu, Pingnan Xiao, Ruimin Hong, Huijun Xu, Jiazhen Cui, Simao Huang, Guoqing Wei, Delin Kong, Jia Geng, Alex H Chang, He Huang, Yongxian Hu

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引用次数: 0

Abstract

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.

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序贯CD19和CD22 CAR-T治疗复发/难治性成人b细胞急性淋巴细胞白血病疗效突出，安全性好。

背景：序贯CD19和CD22嵌合抗原受体(CAR)-T细胞治疗为复发/难治性（R/R） b细胞急性淋巴细胞白血病（B-ALL）的抗原丢失复发提供了一种有希望的方法；然而，对成人的研究仍然有限。方法：本研究旨在评估2020年11月至2023年11月期间，CD19和CD22 CAR-T细胞序贯治疗成人R/R B-ALL患者的疗效和安全性（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：23例患者入组，中位年龄为58.1岁（25.9-75.0岁）。43.5%的患者存在高危细胞遗传学和基因组畸变，5例患者基线为髓外疾病（EMD）。两次输注的中位间隔为3.8个月。两次输注后发生≥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%的患者出现细胞因子释放综合征。2例患者在CD19 CAR-T过程中出现2级免疫效应细胞相关神经毒性综合征（ICANS），而在CD22 CAR-T过程中没有ICANS的报道。中位OS未达到，中位随访19.4个月（范围8.7-45.6），而中位LFS为20.8个月。1年OS和LFS分别为91.3%和67.1%，2年OS和LFS分别为58.6%和47.0%。8例患者复发，1年和2年的累计复发率分别为28.6%和42.5%。较高的基线白血病负担（≥64%骨髓母细胞）和EMD的存在分别是不良OS和LFS的重要危险因素。结论：序贯CAR-T细胞疗法在R/R B-ALL中表现出持久的疗效和可管理的安全性，为解决抗原丢失复发和改善高风险成人患者的长期预后提供了可行的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Hematology & Oncology Medicine-Oncology

CiteScore

12.60

自引率

7.30%

发文量

审稿时长

6 weeks

期刊介绍： Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.