P584: venetoclax plus homoharringtonine-based chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial

Background: Acute myeloid leukaemia (AML) patients still have unsatisfactory clinical outcomes. Venetoclax combined with chemotherapy or azacytidine or low-dose cytarabine has shown efficacy in adults with AML. Homoharringtonine is synergistically lethal with venetoclax in acute myeloid leukemia through down regulation with MCL-1. Aims: We aimed to investigate the activity and safety of venetoclax plus homoharringtonine-based induction regimens in adults with AML. Methods: We conducted a two-stage, single-arm, phase 2 trial at four public hospitals in China. We enrolled patients aged 18–60 years with previously untreated de novo AML. Patients received induction treatment with venetoclax (100 mg on day 2, 200 mg on day 3, and 300 mg on days 4–10), homoharringtonine (2 mg/m² on days 1–5), cytarabine (100 mg/m² on days 1–5), and aclarubicin (12 mg/m² on days 1–5) (VHAA regimen). The primary endpoint was the composite complete remission rate [complete remission (CR) plus complete remission with incomplete blood cell count recovery(CRi)] after one cycle of induction treatment, assessed in the as-treated population. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events. This trial is ongoing and is registered with Chinese Clinical Trial Registry, ChiCTR2100053516. Results: Between Nov 25, 2021, and Mar 23, 2021, 35 patients were assessed for eligibility and 33 were enrolled. 16 (48.5%) patients were men and 17 (51.5%) were women, and all were Asian. The composite complete remission rate after one cycle of DAV regimen was 93.9% (31 of 33 patients, with CR rate of 87.8%, 28/31) in the entire cohort. 31 (100%) of 31 patients had undetectable measurable residual disease (ie, <0.01%). Grade 3 or worse adverse events included neutropenia in 33 (100%) of 33 patients, thrombocytopenia in 33 (100%), anaemia in 33 (100%), febrile neutropenia in 11 (33.3%), pneumonia in eighteen (54.5%), and sepsis in four (12%). No treatment-related deaths occurred. Summary/Conclusion: The VHAA regimen represents an effective induction therapy for newly diagnosed adults with acute myeloid leukaemia, which resulted in a high rate of composite complete remission. These findings showing a safe strategy to incorporate venetoclax combined homoharringtonine-based induction regimens to treat newly diagnosed acute myeloid leukaemia. Keywords: Acute myeloid leukemia, Venetoclax, Chemotherapy, Homoharringtonine