Efficacy of a venetoclax-based, anthracycline-free regimen in newly diagnosed CBFβ::MYH11(+) acute myeloid leukemia

Abstract Background: Induction with cytarabine/anthracycline-based regimen (7+3 regimen) followed by consolidation with high-dose cytarabine (HD Ara-C) remains the standard treatment for newly diagnosed CBFβ::MYH11(+) acute myeloid leukemia (AML). Our previous studies suggested that low-intensity therapy combining venetoclax (Ven) with a hypomethylating agent (HMA) achieved a near 100% remission rate as induction therapy in young, fit patients with CBFβ::MYH11(+) AML; however, data on long-term survival outcomes remain limited. This study aims to evaluate the impact of Ven + HMA as induction therapy in newly diagnosed CBFβ::MYH11(+) AML patients and compare its efficacy with that of the conventional “7+3” regimen. Methods: A retrospective analysis was conducted on 81 newly diagnosed CBFβ::MYH11(+) AML patients treated at The First Affiliated Hospital of Soochow University between January 2017 and June 2025. Among these, 27 patients received Ven + HMA induction therapy, while 54 received the standard “7+3” regimen. All patients who achieved remission underwent consolidation therapy with at least two cycles of HD Ara-C. Subsequent treatment strategies were at the discretion of the treating physician mainly based on measurable residual disease (MRD) status. Treatment response was assessed after each cycle, with MRD monitored using multiparameter flow cytometry (MFC) and real-time quantitative reverse transcriptase-polymerase chain reaction (ABL1 served as the reference gene). MFC MRD was defined as the presence of more than one leukemia cell per 1,000 nucleated bone marrow cells, while complete molecular remission (CMR) was defined as a CBFβ::MYH11/ABL1 ratio of < 0.01% in bone marrow. The probabilities of overall survival (OS) and relapse-free survival (RFS) were estimated via the Kaplan-Meier method.. Results: In the entire cohort of 81 patients, there were 52 males and 29 females, with a median age of 39 years. No significant differences were observed between the two groups in baseline clinical parameters, including initial white blood cell counts, bone marrow blast percentages, or concomitant genetic mutations. Following induction therapy, both groups achieved identical composite complete remission rates (CR+CRi: 96.3%). The MFC-determined MRD negativity rates were 77.7% (21/27) and 72.2% (39/54), respectively, while the median CBFβ::MYH11 transcript levels were 0.385% (range, 0–44.79%) and 0.215% (range, 0–71.15%) (P = 0.06). After two cycles of HD Ara-C consolidation, the median fusion gene transcript levels further declined to 0.05% in both groups (range: 0–0.40% vs. 0–1.1%; P = 0.74). CMR was achieved in 6 (22.2%) and 11 (20.3%) patients in the two groups, respectively (P = 0.85). Subsequently, 7 and 24 patients in the two groups underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), respectively. With a median follow-up of 30 months, relapse occurred in 3 patients (2 molecular relapses) in the Ven + HMA group compared with 16 patients (6 molecular relapses) in the “7+3” group. Five patients died. The causes of death were relapse (1 patient), infection (3 patients) and graft-versus-host disease (1 patient). The 2-year probability of RFS censored at allo-HSCT was 66.0% (95% CI, 50.2–86.9%) in the Ven + HMA group and 53.2% (95% CI, 41.0–69.0%) in the “7+3” group, P =0.44 . No significant differences were observed in estimated 2-year OS between the two cohorts (92.6%, 95% CI, 83.2–100.0% vs. 93.5%, 95% CI, 86.6–100.0%, P = 0.56). As expected, The Ven + HMA regimen demonstrated a lower incidence of grade ≥3 non-hematologic treatment-related adverse events compared to the “7+3” regimen (14.8% vs. 22.2%). Conclusion: The clinical efficacy of the Ven + HMA regimen was non-inferior to the “7+3” regimen, with a more favorable safety profile, providing a novel and effective treatment option for newly diagnosed CBFβ::MYH11(+) AML patients.