The Spectrum of Venetoclax-Based Treatments in Acute Myeloid Leukemia

Background/Objectives: In the recent years there has been a consistent development of clinical studies surrounding the incorporation of the B-cell lymphoma 2 (BCL-2) inhibitor Venetoclax (VEN) into the treatment of acute myeloid leukemia (AML). Methods: A search of literature showed a tremendous development of experimental and clinical studies evaluating the impact of VEN-based regimens in the treatment of AML patients. Results: Recent studies have evaluated VEN-based regimens in newly diagnosed (ND) and refractory/relapsed (R/R) AML patients, showing the efficacy of these treatments. VEN with hypomethylating agents (HMAs) became the standard-of-care for elderly/unfit AML patients. Recent studies strongly support the effectiveness of VEN-based regimens in frontline treatment of adult AML patients eligible for intensive treatments. VEN-based therapies were also used in combination with targeted therapies, thus generating triplet therapeutic regimens that are under evaluation for the treatment of some AML subtypes. However, the response to VEN+HMAs is highly variable and in part depend on tumor genetics; some patients are resistant or relapse following VEN-based treatments and future studies will be required to develop therapeutic strategies able to circumvent resistance and to identify patients at high risk of relapse. Prospective randomized trials are required to establish the real efficacy of VEN in various clinical settings and to refine maintenance and discontinuation strategies, aiming to improve long-term outcomes and to make more safe treatments based on VEN.