Year: 2025
Type: conference-abstract
Abstract: Background: Preliminary studies, including ours, have demonstrated that CAR-T (CAR19) therapy confers suboptimal therapeutic efficacy in high-risk B-cell acute lymphoblastic leukemia (B-ALL), particularly in cases with IKZF1 deletion (IKZF1DEL) and Ph-like phenotype (2023 EHA oral presentation, 2024 Hemasphere). Yet such findings in the Ph-like ALL cohort lack validation in large cohorts. Here we seek to explore the efficacy of CAR19 therapy in high-risk Ph-like ALL. Method: This multicenter, retrospective cohort study included 75 patients with Ph-like ALL in five centers of China from 2017 to 2023. We collected and analyzed the data of clinical characteristics. The event-free survival (EFS) and overall survival (OS) were investigated. Result: A total of 75 patients with Ph-like ALL receiving CAR19 therapy were enrolled. Patients were aged from 6 to 64 years, with the median follow-up time of 445 days (95%CI: 330-559). This cohort was grouped as ABL-class fusions (11/75, 14.6%; ABL1, ABL2, CSF1R, PDGFRB), CRLF2 positive (16/75, 21.3%; rearrangement or high-expression), EPOR or JAK2 rearrangement (8/75, 10.6%), JAK-STAT pathway mutations (16/75, 21.3%; IL7R, SH2B3, JAK1, JAK3, FLT3), Ras pathway mutations only (24/75, 32%; KRAS, NRAS, PTPN11, NF1). Consistent with our previous study, patients with IKZF1 deletion (24/75, 32%) conferred inferior outcome compared with those without (51/75, 68%), with 1y-EFS 14.1% vs. 71.5%, (P=0.002), and 1y-OS 55.7% vs. 80.8% (P=0.22), respectively. Furthermore, within the IKZF1WT group, CAR19 therapy showed different efficacy among various Ph-like subgroups. Synthesized the above findings, patients were further divided into three groups following the survival difference: Standard Risk (SR, IKZF1WTwith ABL1-class fusion or CRLF2 positive, n=18); Medium Risk (MR, IKZF1WT with JAK-STAT pathway mutation or Ras pathway mutation, n=28), and High Risk (HR, IKZF1WT with EPOR or JAK2 rearrangement and IKZF1DEL, n=29). Results demonstrated that HR group showed significantly worse outcomes compared to the other two groups (1y-EFS 79.6% in SR, 73.2% in MR, 12.7% in HR, respectively, P=0.02; 1y-OS 100% in SR, 73.6% in MR, 54.6% in HR, respectively, P=0.018). Conclusion: This study isolated the highest-risk subgroup of Ph-like ALL for CAR19 therapy, which serves as a valuable prognostic feature in Ph-like ALL.
Source: Blood
Authors: Cai Zihong, Bailin He, Baiwei Luo, Zhixiang Wang, Wenhao Zhong, Xuan Zhou, Qifa Liu, Peng Li, Yong-xian Hu, Jing PAN, Liang Huang, Hongsheng Zhou
Institutions: Nanfang Hospital, Southern Medical University, Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, State Key Laboratory of Respiratory Disease, First Affiliated Hospital Zhejiang University, Tongji Hospital, Huazhong University of Science and Technology, Ganzhou People's Hospital
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108480266
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