Venetoclax in acute myeloid leukemia - current and future directions.

B-cell leukemia/lymphoma-2 (BCL-2) inhibition with the targeted oral agent venetoclax (ABT-199) has reshaped the treatment landscape for multiple hematological malignancies. Venetoclax in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) has led to improved outcomes in acute myeloid leukemia (AML) and represents a new standard of care for frontline AML treatment in older patients or those unfit for intensive chemotherapy. Combinations of venetoclax with standard induction therapy or targeted agents such as FLT-3 inhibitors and IDH inhibitors are leading to improved clinical outcomes, representing major advancements in a field that has been without significant changes in treatments for the last 30 years. This review provides biological and clinical rationale for current venetoclax based treatments in AML, addresses common adverse events encountered with venetoclax based therapy, and explores emerging clinical data regarding combinations of novel targeted therapeutics used in conjunction with venetoclax for the treatment of AML.