Introduction: Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. The combination of venetoclax and azacitidine (Ven-Aza) has been approved for the treatment of newly diagnosed AML in patients who are ineligible for intensive chemotherapy based on the VIALE-A trial (ClinicalTrials.gov number, NCT02993523). The LIVEN study (NCT05424562) assesses prospectively real-world outcomes in Canadian patients treated with Ven-Aza.

Methods: Adults ≥ 18 years with newly diagnosed with AML were enrolled. Primary endpoint for the study is overall survival (OS). Data collected included demographics, medical history, cytogenetic and molecular information, concomitant medications, treatment-emergent adverse events (TEAEs), transfusion history, and International Working Group (IWG) response. Patients were risk stratified according to the ELN 2017 classification. The study enrolled 210 patients from 20 sites across Canada.

Results: Participants were enrolled in the study from September 2022 to January 2025. This interim analysis includes 185 patients who were dosed with Ven-Aza and comprise the safety population. The efficacy population includes 144 patients who had at least 1 response assessment.

Median (range) age of the patients was 76 (56-93) years. Over half (57.8%) of patients were over 75 years, and 26.5% were over 80 years. Most patients (69.2%) were male. Comorbidities were common: metabolic in 58.4% and cardiac in 37.8%; prior cancer was reported in 38.4% of the patients. Almost a third of patients (30.3%) had secondary AML (14.0% therapy related, 16.3% prior hematologic malignancy). Of patients with a prior hematologic neoplasm, 10 had a myeloproliferative disorder. Baseline ELN 2017 risk category was adverse in 57.2%, intermediate in 31.7%, and favorable in 11.0% of the patients. Among 106 patients tested for TP53 mutation, 31 (29.2%) were TP53 mutated.

At data cut-off (May 20, 2025), 113 patients had discontinued therapy, while 72 had ongoing treatment. Seventy-six (41.1%) patients have died. With a median follow-up among survivors of 5.6 months, OS was not mature to report. Median (range) of treatment cycles completed was 4 (1-24). Median cycle and Ven treatment length was 30 days and 14 days during cycles 2 to 5, respectively. Concomitant antifungal use was approximately 25% during cycles 1-3, and 15% during cycle 4 and onwards. Median daily dose of Ven was 325 mg and 382 mg during cycles 2 and 3; it subsequently increased to 400 mg during cycles 4 and onwards.

Composite complete response (complete response/complete response with incomplete bone marrow recovery [CR/CRi]) was achieved in 96/144 (66.7%) of patients. Median (IQR) time to response was 71 (53-108) days. Among patients with favorable, intermediate and adverse ELN 2017 risk categories, composite CR was reported in 69.2%, 67.5% and 66.7%, respectively. Further, patients with and without TP53 mutation had a CR/CRi of 65.4% and 71.0%, respectively.

Overall, 39 patients (27.1%) received concomitant granulocyte colony-stimulating factor (G-CSF) during treatment; these patients had a numerically higher composite CR (76.9%) compared to patients who did not receive G-CSF (62.9%). Median number of treatment cycles completed was 5.0 and 4.0 for patients who did and did not use G-CSF, respectively.

Grade ≥3 TEAEs occurred in 133/185 (71.9%) of patients. Hematological Grade ≥3 TEAEs were experienced by 123/185 (66.5%) of patients: neutropenia (45.4%), thrombocytopenia (35.1%), anemia (27.6%), and lymphopenia (23.8%). Sixty (32.4%) patients experienced Grade ≥3 febrile neutropenia; 34 and 26 patients experienced febrile neutropenia during cycle 1 and cycle 2 and onwards, respectively. Serious TEAEs were experienced by 82/185 (44.3%) of the patients, with febrile neutropenia being the most common. Thirty (16.2%) patients experienced a TEAE leading to death.

Conclusion: This prospective study in routine Canadian care of AML with Ven-Aza reports a response rate that is comparable to the VIALE-A trial (64.7%) in a relatively poor-risk cohort, including similar rates in patients with TP53 mutation. Early treatment patterns indicate potentially more treatment cycles were given to patients who had concomitant G-CSF use. With longer follow-up, the duration of response and OS will be reported.

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2025
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