Peng Xiaohuan, Yu Jianing, Tang Futian, Li Yanhong, Bai Jun, Li Lijuan, Zhang Liansheng
Department of Hematology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
Key Laboratory of the Hematology of Gansu Province, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
Discov Oncol. 2024 Sep 17;15(1):451. doi: 10.1007/s12672-024-01348-8.
Acute myeloid leukemia (AML) is a malignant clonal proliferative disease with a high mortality rate. The combination therapy of BCL-2 inhibitor Venetoclax (VEN) and hypomethylating agents (HMAs) has significant anti-leukemia activity.
We analyzed the efficacy, safety and immune response characteristics of AML patients who were unfit for high-dose chemotherapy and accepted the medication of VEN + HMAs.
After VEN + HMAs treatment, 31 newly diagnosed AML patients had the morphologic leukemia-free state rate (MLFS%) of 80.6% (25/31), complete response rate (CR%) of 54.8% (17/31), the minimal residual disease negative rate (MRD-%) of 51.6% (16/31), and the median progression-free survival (PFS) of 14 months. After treatment, the proportion of bone marrow primitive cells, the MRD level, white blood cell (WBC) count, fibrinogen (FIB) level and the proportion of B cells were significantly decreased. The red blood cell (RBC) count, hemoglobin (HGB) level, platelet count (PLT) count, activated partial thromboplastin time (APTT), the proportion of total T cells, CD8 + T cells and the IFN-γ level were significantly increased. After VEN + HMAs treatment, 12 relapsed AML patients had a MLFS% of 50% (6/12), CR% of 33.3% (4/12), MRD-% of 25% (3/12), and a median PFS of 7 months. After treatment, the proportion of bone marrow primitive cells and MRD level were slightly decreased, the proportions of CD8 + T cells and NK cells were significantly increased, the proportion of B cells and IL-10 level were significantly decreased. 12 AML patients who receive microtransplantation (MST) treatment using VEN + HMAs as a pretreatment regimen had a PFS of 20.5 months, which was much greater than VEN + HMAs group alone. Hematological recovery was better in the MST group with significantly increased RBC count, HGB level and PLT count. The most common adverse events were myelosuppression, agranulocytosis, infection and cardiovascular toxicity. No fatal adverse events were reported.
The combination of BCL-2 inhibitors and HMAs had good efficacy and safety in AML patients who were unfit for high-dose chemotherapy, which may improve the immune microenvironment and enhance anti-leukemia immune response.
急性髓系白血病（AML）是一种死亡率高的恶性克隆增殖性疾病。BCL-2抑制剂维奈克拉（VEN）与去甲基化药物（HMAs）联合治疗具有显著的抗白血病活性。
我们分析了不适合接受大剂量化疗且接受VEN + HMAs治疗的AML患者的疗效、安全性和免疫反应特征。
VEN + HMAs治疗后，31例新诊断的AML患者的形态学无白血病状态率（MLFS%）为80.6%（25/31），完全缓解率（CR%）为54.8%（17/31），微小残留病阴性率（MRD-%）为51.6%（16/31），中位无进展生存期（PFS）为14个月。治疗后，骨髓原始细胞比例、MRD水平、白细胞（WBC）计数、纤维蛋白原（FIB）水平和B细胞比例显著降低。红细胞（RBC）计数、血红蛋白（HGB）水平、血小板计数（PLT）、活化部分凝血活酶时间（APTT）、总T细胞比例、CD8 + T细胞比例和IFN-γ水平显著升高。VEN + HMAs治疗后，12例复发AML患者的MLFS%为50%（6/12），CR%为33.3%（4/12），MRD-%为25%（3/12），中位PFS为7个月。治疗后，骨髓原始细胞比例和MRD水平略有降低，CD8 + T细胞和NK细胞比例显著升高，B细胞比例和IL-10水平显著降低。12例以VEN + HMAs作为预处理方案接受微移植（MST）治疗的AML患者的PFS为20.5个月，远高于单独使用VEN + HMAs组。MST组血液学恢复更好，RBC计数、HGB水平和PLT计数显著增加。最常见的不良事件是骨髓抑制、粒细胞缺乏、感染和心血管毒性。未报告致命不良事件。
BCL-2抑制剂与HMAs联合应用于不适合大剂量化疗的AML患者具有良好的疗效和安全性，可能改善免疫微环境并增强抗白血病免疫反应。
