西达本胺联合CAG及维奈克拉-阿扎胞苷治疗新诊断老年急性髓系白血病的2期研究
Phase 2 study of chidamide in combination with CAG and venetoclax-azacitidine in older patients with newly diagnosed acute myeloid leukemia.
作者信息
Liu Qingyang, Yang Jingjing, Lv Lei, Zhang Xiawei, Li Meng, Xu Lingmin, Huang Sai, Jing Yu, Dou Liping
机构信息
State Key Laboratory of Experimental Hematology, Senior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Medical School of Chinese PLA, Beijing, China.
出版信息
Front Immunol. 2025 Feb 26;16:1525110. doi: 10.3389/fimmu.2025.1525110. eCollection 2025.
INTRODUCTION
Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. DNA methyltransferases (DNMTs) and histone-deacetylases (HDACs) are key regulators of gene expression in cells and have been investigated as important therapeutic targets. However, their effects remains unclear as induction therapy for AML.
METHODS
Previously untreated AML patients aged 60 years and over (N=40) were enrolled into this single arm, open-label, phase 2 study to evaluate the clinical efficacy and safety of chidamide combined with CAG and venetoclax-azacitidine (referred to as CACAG-VEN) in elderly AML patients (ClinicalTrials.gov:NCT05659992). All patients received induction treatment with aclarubicin (10 mg/m2/d on days 1, 3, and 5), azacitidine (75 mg/m2 on days 1-7), cytarabine (75 mg/m2 bid on days 1-5), chidamide (30 mg, twice/week for 2 weeks), and venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on days 3-14). Granulocyte colony-stimulating factor 5 mg/kg/day was administered.
RESULTS
Theoverall response rate was 97.5%, with a composite complete response (CRc) rate of 85.0% after one cycle of CACAG-VEN. Patients with adverse risk according to the ELN guidelines had CRc rates of 81.3%. No patients experienced early death within 30 days of therapy initiation. Grade 3 - 4 non-hematological adverse events included febrile neutropenia in 15 (37.5%) of 40 patients, pneumonia in three (7.5%), sepsis in two (5.0%) and blood bilirubin increase in one (2.5%). The 12-month overall survival rate was 73.4% (95% CI: 55.9-84.8%). The median time to recovery was 15.0 (IQR 10.0-19.5) days for platelets ≥ 20000/mL and 13.0 (IQR 10.5-17.0) days for an absolute neutrophil count ≥ 1000 cells/mL after induction therapy.
DISCUSSION
In conclusion, chidamide in combination with CAG and venetoclaxazacitidine was effective and well tolerated in elderly patients with AML.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov/, identifier NCT05659992.
引言
老年急性髓系白血病（AML）患者对标准诱导治疗反应不佳。DNA甲基转移酶（DNMTs）和组蛋白去乙酰化酶（HDACs）是细胞中基因表达的关键调节因子，已被作为重要的治疗靶点进行研究。然而，它们作为AML诱导治疗的效果仍不明确。
方法
将60岁及以上未经治疗的AML患者（N = 40）纳入这项单臂、开放标签的2期研究，以评估西达本胺联合CAG和维奈克拉-阿扎胞苷（简称CACAG-VEN）在老年AML患者中的临床疗效和安全性（ClinicalTrials.gov：NCT05659992）。所有患者接受阿克拉霉素（第1、3和5天，10 mg/m²/天）、阿扎胞苷（第1 - 7天，75 mg/m²）、阿糖胞苷（第1 - 5天，75 mg/m²，每日两次）、西达本胺（30 mg，每周两次，共2周）和维奈克拉（第1天100 mg，第2天200 mg，第3 - 14天400 mg）的诱导治疗。给予粒细胞集落刺激因子5 mg/kg/天。
结果
总体缓解率为97.5%，一个周期的CACAG-VEN治疗后复合完全缓解（CRc）率为85.0%。根据ELN指南具有不良风险的患者CRc率为81.3%。没有患者在治疗开始后30天内发生早期死亡。3 - 4级非血液学不良事件包括40例患者中有15例（37.5%）发生发热性中性粒细胞减少、3例（7.5%）发生肺炎、2例（5.0%）发生败血症和1例（2.5%）血胆红素升高。12个月总生存率为
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