How I treat patients with AML using azacitidine and venetoclax

Venetoclax (VEN) received full approval in October 2020 for use in older patients who are unfit with acute myeloid leukemia (AML) combined with either hypomethylating agents or low-dose cytarabine. This ended a semicentennial of stalled clinical progress and initiated a new treatment option with proven capacity to enhance response and prolong survival in older patients with AML. Despite widespread use of azacitidine-VEN (AZA-VEN), there is increasing appreciation that this regimen is myelosuppressive and associated with a higher risk of infectious complications than AZA alone. Key principles of initial management include prevention of tumor lysis syndrome in patients at high risk and minimizing infectious complications during induction. In the postremission phase, limiting cumulative marrow suppression by allowing sufficient time between cycles for optimal marrow recovery and truncating the duration of VEN exposure for those with delayed blood count recovery have emerged as important axioms of effective care. This article casts a clinical spotlight on important challenges and dilemmas encountered in practice. We also outline a structured framework to assist in the safe management of AZA-VEN in the clinic.