Canadian Real-World Data for Acute Myeloid Leukemia Chemotherapy-Ineligible Patients on Venetoclax: An Interim Analysis from the Prospective Liven Study

Introduction: Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and has the lowest survival rate. Recent advances in AML therapies have led to improvements in patient outcomes. The objective of the prospective observational LIVEN study is to assess real-world clinical outcomes in Canadian patients with AML who are ineligible for intensive induction chemotherapy and treated first-line with venetoclax combination therapy with azacitidine [AZA] or low-dose cytarabine [LDAC] in inpatient and outpatient settings. Methods: Adults ≥ 18 years diagnosed with AML were enrolled following the decision to treat with venetoclax combination therapy. Patients provided written informed consent; collected data includes demographics, medical history, cytogenetic and molecular testing, tumor lysis syndrome (TLS) risk, concomitant treatments, adverse events, transfusion history, and International Working Group (IWG) response. This ongoing study will enroll approximately 200 patients from 20 sites across Canada. Primary endpoint for the study is overall survival. Interim analysis data were analyzed descriptively for quantitative variables. Complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi) as per modified IWG criteria and incidence of treatment-emergent adverse events (TEAEs) were evaluated. Results: Sixty patients were included in this interim analysis, 59 dosed with venetoclax + AZA and 1 dosed with venetoclax + LDAC. The interim analysis included patients who had completed Cycle 3 through March 2024; expanded data is forthcoming as the study progresses. Patient ages ranged from 59 to 87 years, with a mean (SD) age of 74.6 (6.2). Over half (55.0%) of patients were over 75 years, and 23.3% were over 80 years. The majority of patients (68.3%) were male. 35.0% of patients had an ECOG-PS score of 0 or 1 and 20.0% had a score of ≥2 at baseline; for 45.0% of patients, baseline ECOG-PS score was not available. Distribution of patients by region was 40.0% in the West, 26.7% in Ontario, 13.3% in Québec, and 20.0% in the Atlantic. In the venetoclax + AZA cohort, 13 (22.0%) of patients received fluconazole, 5 (8.5%) received posaconazole, and 2 (3.4%) received voriconazole as prophylactic therapy. Overall, 36/51 (70.6%) patients had response assessments during Cycles 1, 2, and/or 3; of these evaluable patients, CR/CRi was achieved by 19/36 (52.8%) receiving venetoclax + AZA. In Cycle 1 CR/CRi was achieved by 12/28 patients (42.9%), in Cycle 2 by 10/19 patients (52.6%) and in Cycle 3 by 10/16 (62.5%) patients. The 1 patient who received venetoclax + LDAC did not have an assessment for CR/CRi. Bone marrow assessments were available for 47/59 (79.7%) of patients across Cycles 1 to 3; 34/59 (57.6%) in Cycle 1, 15/49 (30.6%) in Cycle 2, and 10/47 (21.3%) of patients in Cycle 3. Overall, 9 patients (15.3%) received granulocyte colony stimulating factors during Cycles 1, 2, and 3. Transfusion independence was reported for 52.0% of patients. Incidence of any TEAE occurred in 71.2% of patients receiving venetoclax + AZA. Serious TEAEs occurred in 42.4% of patients, febrile neutropenia was the most common serious TEAE (10.2%). Hematological TEAEs were more common than non-hematological events, 61.0% versus 40.7%; the most common hematological events were neutrophil count and platelet count decreased (27.1% each) and the most common non-hematological event was hypokalemia (6.8%). In Cycle 1, 3 patients receiving venetoclax + AZA met criteria for laboratory TLS per Howard criteria and 0 patients met criteria for clinical TLS. These patients did not discontinue venetoclax +AZA . Within the venetoclax + AZA cohort, in Cycles 1, 2, and 3, most patients (86.4%) had a venetoclax dosing duration of >21 days per 28-day cycle (overall range of 7 to 125 days). In Cycle 1, the mean duration of venetoclax treatment was 23.5 days with a mean daily dose of 254.2 mg. In Cycle 2, the mean duration of venetoclax treatment was 19.8 days with a mean daily dose of 302.4 mg. In Cycle 3, mean duration of venetoclax treatment was 18.6 days with a mean daily dose of 293.6 mg. Conclusion: This interim analysis reports data on the first 60 patients treated in Canadian practices with venetoclax from the prospective real-world LIVEN study. The safety profile is consistent with prior studies of venetoclax combination therapies, and cytopenia/neutropenia was managed by dose modifications.

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