Yin Jia, Cui Qing-Ya, Dai Hai-Ping, Qu Chang-Ju, Li Zheng, Kang Li-Qing, Cui Wei, Tian Xiao-Peng, Zhu Xia-Ming, Yu Lei, Wu De-Pei, Tang Xiao-Wen
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
J Hematol Oncol. 2025 May 6;18(1):53. doi: 10.1186/s13045-025-01708-z.
Approximately 78.3% of patients with t(8;21) acute myeloid leukemia (AML) express CD19, making it a potential target for chimeric antigen receptor (CAR)-T cell therapy focused on CD19. This prospective phase II trial (NCT03896854) evaluated the safety and efficacy of CD19 CAR-T cell treatment in 10 relapsed CD19-positive t(8;21) AML patients. This study enrolled eight patients with hematologic and two with molecular relapsed AML. The median bone marrow blast percentage was 12.4% (0.1-50.2%), and the blasts exhibited a median CD19 positivity of 55.7% (22.6-97.1%). Genetic profiling revealed TP53 alterations (n = 1), KIT (n = 3) and FLT3-ITD (n = 1) mutations. After lymphodepletion with fludarabine and cyclophosphamide (FC), 5-20 × 10 cells per kilogram of CAR-T cells were administered. All patients experienced grade 3 or higher hematologic toxicities following tumor-reduction chemotherapy and the FC regimen, which were managed for a median of two weeks after CAR-T treatment. Non-hematological toxicities were mild and reversible. Eight patients presented with mild (grade 1-2) cytokine release syndrome (CRS), and one experienced grade 3 CRS. The immune effector cell-associated neurotoxicity syndrome was not observed. All patients achieved complete remission (CR) after CAR-T, with 60% achieving a molecularly MRD-negative CR. RUNX1::RUNX1T1 fusion transcript levels demonstrated a median 2.5-log reduction (range: 0.7-4.5 log; P = 0.002). At a median follow-up of 64.6 months (range: 11.2-88.8 months), the median overall survival and leukemia-free survival were 11.6 and 3.8 months, respectively. The 12-month cumulative incidence of relapse was 53.3%. These findings indicated that CD19 CAR-T was a safe and effective option for relapsed CD19-positive t(8;21) AML.
约78.3%的t(8;21)急性髓系白血病（AML）患者表达CD19，这使其成为针对CD19的嵌合抗原受体（CAR）-T细胞疗法的潜在靶点。这项前瞻性II期试验（NCT03896854）评估了CD19 CAR-T细胞治疗10例复发的CD19阳性t(8;21) AML患者的安全性和疗效。本研究纳入了8例血液学复发和2例分子学复发的AML患者。骨髓原始细胞百分比中位数为12.4%（0.1 - 50.2%），原始细胞的CD19阳性率中位数为55.7%（22.6 - 97.1%）。基因分析显示TP53改变（n = 1）、KIT（n = 3）和FLT3 - ITD（n = 1）突变。在用氟达拉滨和环磷酰胺（FC）进行淋巴细胞清除后，每千克给予5 - 20×10个CAR-T细胞。所有患者在肿瘤减量化疗和FC方案后均经历了3级或更高等级的血液学毒性，在CAR-T治疗后中位处理了两周。非血液学毒性轻微且可逆。8例患者出现轻度（1 - 2级）细胞因子释放综合征（CRS），1例经历3级CRS。未观察到免疫效应细胞相关神经毒性综合征。所有患者在CAR-T治疗后均达到完全缓解（CR），60%达到分子学微小残留病阴性CR。RUNX1::RUNX1T1融合转录本水平显示中位数降低2.5个对数（范围：0.7 - 4.5对数；P = 0.002）。在中位随访64.6个月（范围：11.2 - 88.8个月）时，总生存中位数和无白血病生存中位数分别为11.6个月和3.8个月。12个月的累积复发率为53.3%。这些发现表明，CD19 CAR-T是复发的CD19阳性t(8;21) AML的一种安全有效的选择。
