Dasatinib and CAR T-Cell Therapy in Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

作者：Mingming Zhang, Shan Fu, Jingjing Feng, Ruimin Hong, Guoqing Wei, Houli Zhao, Mengyu Zhao, Huijun Xu, Jiazhen Cui, Simao Huang, Xiaoyu Wu, Lianxuan Liu, Jie Sun, Wenjun Wu, Yuanyuan Zhu, Jingsong He, Yi Zhao, Zhen Cai, Weiyan Zheng, Xiujin Ye, Jimin Shi, Yi Luo, Dongrui Wang, Alex H. Chang, Yongxian Hu, He Huang · 发表于：JAMA Oncology · 年份：2025 · DOI：10.1001/jamaoncol.2025.0674 · 被引用次数：27 · 研究领域：CAR-T cell therapy research、Chronic Myeloid Leukemia Treatments、Acute Lymphoblastic Leukemia research

Importance: A combination of tyrosine kinase inhibitors and chimeric antigen receptor (CAR) T cells has made a breakthrough in refractory or relapsed Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, it remains unclear if this treatment in newly diagnosed Ph-positive ALL is associated with high rates of complete molecular remission (CMR) and leukemia-free survival. Objective: To evaluate the efficacy and safety of dasatinib in combination with CAR T cells as frontline therapy in adults with newly diagnosed Ph-positive ALL. Design, Setting, and Participants: This trial was conducted at a single center, the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were enrolled in this phase 2, single-arm nonrandomized clinical trial between March 5, 2021, and April 13, 2024. The data cutoff date was February 10, 2025. The data analysis was conducted on February 11, 2025. The median duration of follow-up was 23.9 (range, 7.3-47.7) months. A total of 29 adults with newly diagnosed Ph-positive ALL and adequate organ function were screened for eligibility, and 1 patient who received a diagnosis of blast-phase chronic myeloid leukemia was excluded. Intervention: Dasatinib was administered with a 2-week vindesine and dexamethasone regimen as induction, followed by sequential CD19 and CD22 CAR T-cell therapies and single-agent dasatinib maintenance. Main Outcomes and Measures: The primary end point was CMR rate after CD19 CAR T-cel...