Single-Center Retrospective Clinical Evaluation of 7-Day Venetoclax Combined with Decitabine and CAG Regimen for AML Older Than 60 Years

Background: Even though VIALE-A study demonstrated that combination treatment with venetoclax plus azacitidine induced a composite complete remission rate of 66.4% in newly diagnosed elderly AML patients, there is still an unmet clinical need and room for improvement. Firstly, 30-40% of patients still fail to achieve remission. Secondly, how to increase the depth of remission and obtain a higher MRD negative rate without increasing the toxicity response is the current direction of clinical research. Our retrospective analysis found that the 7-day short-term venetoclax combiend with decitabine and CAG (G-CSF priming, low dose cytarabine and aclarubincin ) induction chemotherapy induced higher remission rates and higher MRD-negativity rates compared with the venetoclax plus azacitidine (VA) regimen in in newly diagnosed AML patients older than 60 years. Methods: We retrospectively analysed the outcomes of the newly diagnosed AML patients aged 60 years or older who received VD-CAG and VA regimen at the West China Hospital of Sichuan University from November 2021 to September 2023. VD-CAG regimen was administered as follows: venetoclax orally once daily (100mg on day 1, 200mg on day 2, 400mg on days 3-9), decitabine 20 mg/m2 intravenously on days 1-5, cytarabine 10 mg/m2 subcutaneously q12h on days 3-9, aclacinomycin 10 mg/m2 intravenously on days 3-6, G-CSF 300 μg /d subcutaneously on days 0 -9. For patients with leukocytosis, hydroxyurea was given orally until the WBC count dropped below 10×10 9 /L, and then the chemotherapy was initiated. VA regimen was administered as venetoclax orally once daily (100mg on day 1, 200mg on day 2, 400mg on days 3-28) and azacitidine 75 mg/m2 subcutaneously on days 1-7. Venetoclax dose was adjusted based on concomitant CYP3A inhibitors. The efficacy was evaluated by bone marrow morphology and multiparameter flow cytometry (MFC). The primary endpoints were composite complete remission rate (CR plus CRi), MRD negative and safety. Results: Twenty-three patients received VD-CAG induction chemotherapy with a median age 68 years (IQR, 60-75 years), including 8 (34.8%) in low-risk, 8 (34.8%) in intermediate-risk and 7 (30.4%) in the high-risk group. Twenty-four patients received VA induction chemotherapy with a median age 73 years (IQR, 69-76 years), including 2 (8.3%) in low-risk, 6 (25%) in intermediate-risk and 16 (66.7%) in the high-risk group. At the end of one course of induction, the VD-CAG and VA groups had comparable composite remission rates (95.2% versus 88.9%, p=0.4582), but the VD-CAG group had a higher MFC-MRD negative rate (85% versus 50%, p=0.0235). There was no significant difference between the VD-CAG and VA regimens for the most common adverse events grade 3 to 4 myelosuppression (100% versus 95.83%, p=0.3224) and pulmonary infection (39.13% versus 54.17%, p=0.3017). The median leukocyte recovery time (15 days vs. 22 days, p=0.0698), platelet recovery time (13 days vs. 7 days, p=0.3187), erythrocyte transfusion (8 units vs. 5.5 units, p=0.5228), and platelet transfusion (4 units vs. 4.5 units, p=0.5452) were comparable between the VD-CAG and VA groups. As of 31 March 2024, with a median follow-up of 9 months, median overall survival was not reached in the VD-CAGgroup, and median overall survival was 9 months (95% CI 6 to 16) in the VA group (risk ratio 0.4482, 95% CI 0.1685 to 1.192). Conclusion: the 7-day short-term venetoclax combiend with decitabine and CAG regimen is effective in the treatment of AML older than 60 years. The therapy was able to induce deeper remission, and improve long-term survival rate, with a safety profile not significantly different from that of the VA regimen. It is worth clinical promotion.

No relevant conflicts of interest to declare.