Combination of Venetoclax and Azacytidine As First-Line Induction Therapy for Acute Myeloid Leukemia in Patients Younger Than 60 Years: A Tertiary Care Center Experience from Our Low Middle Income Country

INTRODUCTION: Anthracycline- and cytarabine-based “7+3” induction chemotherapy has been the frontline treatment option for acute myeloid leukemia (AML) in the non-elderly and fit patient population. Sixty percent of these patients (pts) achieve Complete remission (CR). However, an estimated 30-40% of pts relapse (Tara L. Lin & Livio Pagano et al., Expert Review of Hematology, 2021). In addition, based on a large US database study and studies from India, the “7+3” regimen is associated with high rates of induction mortality, intensive care unit (ICU) admission, and duration of hospital stay. BCL2 inhibition with venetoclax has been a new paradigm for the treatment of AML. Herein, we present our institutional experience in treating AML in pts younger than 60 years (yrs) old with a combination of venetoclax (ven) and azacytidine (aza). METHODS: We conducted a retrospective review of patients aged 18-60 who were newly diagnosed with AML between May 2020 and May 2023, and in this study, we included all pts, who met the WHO criteria for AML, did not have APML, had no prior history of treatment for other malignancies, and had not received prior induction treatment. Pts received aza 75 mg/m2 on days 1-7 and ven, which escalated from 100 to 200 to 400 mg on days 1-3. Ven continued at 400 mg without posaconazole or 100 mg with posaconazole from days 4-28, and bone marrow aspiration and biopsy were performed after day 28. Patients who achieved morphological remission without count recovery had up to 14 days off therapy before subsequent cycles. Non-responders received up to 1-2 additional cycles. Post-response (defined as a complete remission [CR] ), and patients with measurable residual disease (MRD) negative by multiparameter flow cytometry (MFC) with the residual blast cutoff being < 0.1% proceeded to further cycles. The primary objective of the study is to focus on the induction mortality rate and complete remission in younger, newly diagnosed AML pts who received aza and ven in the induction period. Responses to induction and subsequent post-remission therapy were recorded. RESULTS: A total of 17 patients with AML aged ≥ 18 years and ≤60 years were treated with a combination of aza and ven from May 2020 to May 2023. The median patient age was 47 yrs (interquartile range [IQR]: 30-56 yrs, 52.9% age