Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Blood Cancer J. 2020 Nov 23;10(11):122. doi: 10.1038/s41408-020-00388-x.
Venetoclax (VEN), a small-molecule inhibitor of B cell leukemia/lymphoma-2, is now FDA approved (November 2018) for use in acute myeloid leukemia (AML), specific to newly diagnosed elderly or unfit patients, in combination with a hypomethylating agent (HMA; including azacitidine or decitabine) or low-dose cytarabine. A recent phase-3 study compared VEN combined with either azacitidine or placebo, in the aforementioned study population; the complete remission (CR) and CR with incomplete count recovery (CRi) rates were 28.3% and 66.4%, respectively, and an improvement in overall survival was also demonstrated. VEN-based chemotherapy has also shown activity in relapsed/refractory AML (CR/CRi rates of 33-46%), high-risk myelodysplastic syndromes (CR 39% in treatment naïve, 5-14% in HMA failure), and blast-phase myeloproliferative neoplasm (CR 25%); in all instances, an additional fraction of patients met less stringent criteria for overall response. Regardless, venetoclax-induced remissions were often short-lived (less than a year) but long enough to allow some patients transition to allogeneic stem cell transplant. Herein, we review the current literature on the use of VEN-based combination therapy in both acute and chronic myeloid malignancies and also provide an outline of procedures we follow at our institution for drug administration, monitoring of adverse events and dose adjustments.
维奈托克（VEN）是一种 B 细胞白血病/淋巴瘤-2 的小分子抑制剂，现已获得美国食品和药物管理局（FDA）批准（2018 年 11 月），用于治疗新诊断的老年或不适合治疗的急性髓细胞白血病（AML），与低甲基化剂（HMA；包括阿扎胞苷或地西他滨）或低剂量阿糖胞苷联合使用。最近的一项 3 期研究比较了 VEN 联合阿扎胞苷或安慰剂在上述研究人群中的疗效；完全缓解（CR）和不完全血细胞计数恢复的完全缓解（CRi）率分别为 28.3%和 66.4%，并且总体生存也得到了改善。基于 VEN 的化疗在复发性/难治性 AML（CR/CRi 率为 33-46%）、高危骨髓增生异常综合征（初治患者的 CR 为 39%，HMA 失败患者为 5-14%）和急变期骨髓增殖性肿瘤（CR 为 25%）中也显示出活性；在所有情况下，都有更多的患者符合总体反应的不太严格的标准。无论如何，维奈托克诱导的缓解往往是短暂的（不到一年），但足以使一些患者过渡到异基因干细胞移植。在此，我们回顾了 VEN 联合治疗在急性和慢性髓性恶性肿瘤中的应用的现有文献，并提供了我们在机构中进行药物管理、监测不良反应和剂量调整的程序概述。
