BCL-2 inhibitor venetoclax-innovating the therapeutic pattern of acute myeloid leukemia

Abstract

Acute myeloid leukemia （AML） is a kind of myeloid clonal proliferative tumor with strong heterogeneity. Chemotherapy and hematopoietic stem cell transplantation are the main treatment methods for AML. Although patients can achieve better therapeutic effects, the elderly people cannot tolerate conventional chemotherapy due to many reasons such as advanced age, physiological and cognitive impairment, and increased complications, with limited treatment options and shorter survival period （only 2 months）. Venetoclax is the first approved B-cell lymphoma/leukemia-2 inhibitor （BCL-2） in the world. Many studies have shown that hypomethylating agents (HMA) such as azacytidine or dexcitabine and other low-intensity chemotherapy regimens combined with venetoclax has good efficacy in elderly patients, significantly improving combined overall response rate and overall survival （CR/Cri 66.4%, median OS 14.7 months）, enable more patients to transition to the allogeneic hematopoietic stem cell transplantation stage （allo-HSCT）. This article briefly reviews the mechanism of action of venetoclax, its clinical application in AML and some related issues including drug resistance.

Keywords

• b-cell lymphoma/leukemia-2 inhibitor
• non-chemotherapeutic agents
• acute myeloid leukemia
• venetoclax
• targeted therapy
• demethylated drugs
• azacytidine
• dexcitabine