INTRODUCTION: We aimed to compare outcomes of patients with AML treated with frontline hypomethylating agent and venetoclax (HMA + Ven) who achieved complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) as defined by ELN 2022. METHODS: Patients with AML seen at Moffitt Cancer Center between 2018 and 2022 and treated with HMA + Ven were retrospectively evaluated. RESULTS: About 120 patients achieved blast clearance with best response of CR in 52 (43.3%), CRh in 22 (18.3%), CRi in 31 (25.8%) and MLFS in 15 (12.5%) patients. Greater proportion of patients with MLFS had a prior myeloid malignancy (p = 0.003) and were treated with prior HMA (p <
0.001). Patients that achieved MLFS as their best response had inferior OS compared to the CR/CRh/CRi cohort (8 months vs. 27 months
p <
0.001). RFS was also worse for the MLFS cohort. CONCLUSION: To the best of our knowledge, this is the largest study analyzing differences in outcomes of AML patients treated with HMA + Ven based on best response. We noted that prior myeloid malignancy and use of HMA led to more MLFS as best response compared to CR/CRi. The OS and RFS were inferior for MLFS cohort.