AML-703 Feasibility of Azacitidine and Venetoclax Followed by High/Intermediate Dose Cytarabine (HIDAC/IDAC) Consolidation in Previously Untreated Acute Myeloid Leukemia Patients Unfit for Intensive Chemotherapy in a Resource Constraint Low-Middle In

Acute myeloid leukemia (AML) predominantly affects the elderly, posing challenges in treatment due to comorbidities and age-related factors. Azacitidine and venetoclax have shown promising results in older or unfit AML patients. However, the feasibility and efficacy of consolidative therapy with high/intermediate-dose cytarabine (HIDAC/IDAC) following azacitidine and venetoclax induction in this population remain unexplored. Cytarabine consolidation remains relevant in most of the low-middle income countries, as bone marrow transplantation is not always feasible. This ambispective non-randomized interventional study was designed to evaluate the feasibility and outcomes of azacitidine and venetoclax induction followed by HIDAC/IDAC consolidation in previously untreated, unfit AML patients. Eligible patients, aged >14 years, deemed ineligible for standard chemotherapy, received azacitidine and venetoclax induction therapy. Consolidation with HIDAC/IDAC was offered to those achieving remission. Primary objectives included overall survival (OS) and progression-free survival (PFS), while secondary objectives encompassed comparison with continuous azacitidine and venetoclax therapy and barriers to administration of HIDAC/IDAC consolidation. During the study period, out of 198 AML patients admitted, 48 deemed unfit for intensive chemotherapy received azacitidine and venetoclax (AZA-VEN) induction therapy, with 77% presenting baseline infections. Twenty-two patients achieved remission, of whom 9 received HIDAC/IDAC consolidation, while 13 continued AZA-VEN therapy. In the AZA-VEN-HIDAC group, median overall survival (OS) was 21 months, compared to 15 months in the AZA-VEN group (p=0.082%). Median progression-free survival (PFS) was 21 months in both groups (p=0.65%). Barriers to cytarabine consolidation included patient unwillingness for prolonged hospitalization and persistence or emergence of new infections beyond induction therapy. Among unfit treatment naive AML patients, who achieve remission with AZA-VEN, there was no significant difference in OS and PFS between those treated with HIDAC/IDAC consolidation and those receiving continuous AZA-VEN therapy.