AML-272: Real-World Experience with Venetoclax-Based Regimens for the Treatment of Acute Myeloid Leukemia

Background: Prognosis of acute myeloid leukemia (AML) still represents a clinical challenge, especially in elderly patients. Venetoclax is a selective, potent, orally bioavailable BCL-2 inhibitor that has demonstrated single-agent activity both in relapsed/refractory (R/R) and newly diagnosed AML. However, the efficacy and safety of venetoclax combinations regimens in the “real-life” setting have not been extensively described. We aimed to report our single-center experience of venetoclax alone or in a combination approach for AML patients not eligible for standard induction therapy. Methods and Results: A retrospective analysis has been performed on 39 consecutive patients affected by treatment-naive (n=13) or R/R AML (n=26) treated with venetoclax alone (n=4) or in association with azacitidine (n=31), decitabine (n=3), or low-dose cytarabine (n=1). Median age was 71 years, with 67% older than 65 years. The majority showed an intermediate genetic risk. Sixteen patients (41%) were treated in the salvage-2 setting or later, and 7 (18%) had received a prior allogeneic stem cell transplantation. Venetoclax was administered at a dose of 400 mg daily (n=22), with dose reductions to 200 mg (n=9) or 100 mg (n=8) in cases of concurrent therapy with CYP3A4 inhibitors. The most common grade 3 or 4 toxicities were hematological or infectious (49% and 51%, respectively). Nineteen patients (49%) achieved a complete response, with median time to best response of 1 month. Six-month overall survival (OS) in the treatment-naive and R/R groups were 92% and 45%, respectively (p=0.0186), with no differences among genetic risk groups. Median disease-free survival was 5 months. The estimated 6-month OS was significantly higher in patients who achieved a response, regardless of disease status at the time of starting treatment (p Conclusions: Our real-world data confirmed that venetoclax-based regimens are a viable and safe option for AML patients unfit for intensive chemotherapy in both first-line and salvage settings. Furthermore, the association of venetoclax and hypomethylating agents proved to be a feasible bridging therapy to transplantation in elderly AML patients.