Superior Efficacy and Deep Molecular Remission with Venetoclax Plus Hypomethylating Agent in Elderly Acute Myeloid Leukemia: A Real-World Comparative Cohort Study

Chen Luo,1,2 Yuhan Jiang,1,2 Huiling Yan,2 Kan Sun,3 Wentao Li,3 Mengqing Cao,2 Lijun Zhu,2 Xing Hu,2 Juan Tong,2 Changcheng Zheng1– 3 1Department of Internal Medicine, Graduate School of WanNan Medical College, Wuhu, People’s Republic of China; 2Department of Hematology, Centre for Leading Medicine and Advanced Technologies of IHM, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 3Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Changcheng Zheng, Department of Hematology, Centre for Leading Medicine and Advanced Technologies of IHM, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, 230001, People’s Republic of China, Tel/Fax +86-551-62282990, Email zhengchch1123@ustc.edu.cnBackground: Treatment of elderly acute myeloid leukemia (AML) remains challenging, and intensive chemotherapy is often poorly tolerated in elderly patients due to comorbidities and frailty, thereby necessitating low‑intensity alternatives. This study compared the efficacy and safety of venetoclax combined with a hypomethylating agent (VEN-HMA) against HMA plus low-intensity induction chemotherapy (HMA-LIIC) and low-intensity induction chemotherapy alone (LIIC) in a real-world elderly AML cohort.Methods: In this retrospective study, 136 newly diagnosed elderly AML patients (≥ 60 years) were categorized into three groups: VEN-HMA (n=45), HMA-LIIC (n=38), and LIIC (n=53). LIIC was defined as low‑dose cytarabine ‑based regimens given without a concomitant VEN or HMA. Key endpoints included morphologic response, measurable residual disease (MRD) negativity, early mortality, and overall survival (OS).Results: The VEN-HMA group demonstrated a significantly higher overall response rate (82.2%) than the HMA-LIIC (39.4%) and LIIC (54.7%) groups (p=0.010). While the complete remission (CR) rate was comparable across groups, the VEN-HMA group had a notably higher CR with incomplete hematologic recovery (CRi) rate (33.3% vs 10.5% vs 11.3%) (p=0.007). The MRD negativity rate was significantly superior in the VEN-HMA group (65.5%) compared to HMA-LIIC (18.8%) and LIIC (41.7%) (p=0.010), an advantage particularly pronounced in intermediate-risk patients (68.8% vs 12.5% vs 30.8%, p=0.021). The VEN-HMA group also had a numerically lowest 30-day early mortality (4.44% vs 7.97% vs 17.0%). With a median follow-up, the median OS was 11.0 months in the VEN-HMA group, 7.2 months in the HMA-LIIC group, and 10.1 months in the LIIC group. The VEN-HMA group showed a numerically higher 1-year OS rate (55.0%) than the HMA-LIIC group (35.0%) and comparable to the LIIC group (47.9%) (p=0.153).Conclusion: In this real-world analysis, VEN-HMA demonstrated superior response rates and deeper molecular remissions (MRD) compared to HMA-LIIC and LIIC in elderly AML patients, further supporting its use as an effective and feasible frontline option for this population, especially in the intermediate-risk group.Keywords: venetoclax, hypomethylating agent, low-intensity induction chemotherapy, measurable residual disease, overall survival