Azacitidine in combination with shortened venetoclax treatment cycles in patients with acute myeloid leukemia

Abstract

The combination of venetoclax with hypomethylating agents is currently the standard of care for elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Despite its favorable efficacy, clinical use is often associated with post-remission cytopenia, frequently necessitating treatment delays and dose modifications. This study aims to evaluate the efficacy and safety of shortened venetoclax treatment durations. A multicenter analysis was conducted involving 20 adult AML patients receiving venetoclax (7 or 14 days with 9 and 11 patients, respectively) combined with 5-azacitidine (5-7 days) between 2021 and 2024. The cohort included patients from four German academic centers all treated in first line. Outcome measures included bone marrow response, transfusion dependence, overall survival (OS) and progression-free survival (PFS). Median age was 73.5 years, with 70% of patients having secondary AML. Adverse molecular risk was observed in 75% of patients. The overall response rate (ORR) was 100%, with a composite complete remission rate of 78%. No significant differences in response rates were observed between the 7-day and 14-day venetoclax regimens. Median OS for the cohort was 15 months. Infection-related complications were observed in 55% of patients, with severe sepsis in 20% of cases. In this cohort, shortened venetoclax regimens demonstrated efficacy comparable to standard treatment protocols, with a potential reduction in hematologic toxicity. These findings support the individualization of treatment regimens to optimize clinical outcomes while potentially minimizing adverse effects.

Keywords: 5-azacitidine; 7 + 7; Acute myeloid leukemia; Shortened treatment; Toxicity; Venetoclax.

Fig. 1

a Treatment diagram. Overview about different treatment cohorts and disease settings: * 2 patients without bone marrow assessment. VEN venetoclax; AZA 5-azacytidine; pts patients; ASCT allogeneic stem cell transplantation, 7 + 7 seven days venetoclax + seven days HMA; 7 + 14 seven days HMA + 14 days venetoclax.b Risk stratification. ELN European Leukemia Net; mPRS molecular prognostic risk score

Fig. 2

Response assessment. Bone marrow response rates for indicated patient cohorts at first and best response A-E are illustrated. *2 patients are excluded due to lack of bone marrow response data. ORR Overall response rate; CRc composite complete remission (CR + CRi); CR complete remission; CRi complete remission with incomplete hematological recovery; PR partial remission; sAML secondary acute myeloid leukemia

Fig. 3

Survival analysis. Kaplan-Meier estimates for OS A-C and PFS D are illustrated for indicated treatment cohorts. In E and F, OS and PFS for ELN2022 and in G and H mPRS risk groups are shown.mOS median overall survival; mPFS median progression free survival, ELN European leukemia Net mPRS molecular prognostic risk score