Meta-analysis confirms venetoclax plus decitabine as a frontline game-changer in elderly AML (Acute Myeloid Leukemia)

Abstract

Abstract Background: Acute Myeloid Leukemia (AML) in elderly patients is characterized by poor clinical outcomes, limited tolerance to intensive chemotherapy, and high relapse rates. Epigenetic dysregulation, especially hypermethylation of tumor suppressor genes (HIC-1A, P15, ER), contributes to leukemogenesis and therapeutic resistance. Decitabine (DEC), a hypomethylating agent, has demonstrated clinical activity but limited curative potential as monotherapy. Venetoclax (VEN), a selective BCL-2 (B-cell lymhoma protein) inhibitor, synergizes with DEC to enhance leukemic cell apoptosis. This meta-analysis assesses the efficacy and safety of the VEN + DEC combination in elderly AML patients, incorporating data from multiple trials. Methods: A systematic search of PubMed, EMBASE, Cochrane Library, CNKI identified seven eligible studies. A total of 312 elderly AML patients treated with VEN + DEC were compared to controls (DEC alone or other low-intensity regimens). Outcomes included : -Complete Remission (CR) -Composite Response Rate (CRR) -Overall Response Rate (ORR) -Safety outcomes focused on grade 3/4 adverse events. Odds ratios (ORs) were calculated using random- or fixed-effects models depending on heterogeneity. Results: Efficacy Outcomes Complete Remission: The VEN + DEC group achieved significantly higher CR rates than control (OR = 1.90; 95% CI: 1.36–2.67; p = 0.0002). Composite Response Rate: The pooled data demonstrated a substantial increase in composite response (CR + CRi) with VEN + DEC (OR = 2.29; 95% CI: 1.55–3.42; p = 0.0001). Overall Response Rate: A favorable trend was observed in ORR for VEN + DEC (OR = 2.31; 95% CI: 0.55–5.53), though heterogeneity limited statistical significance. Subgroup Highlights:The most robust CR benefit was seen in patients receiving VEN 400 mg (OR = 1.99; 95% CI: 1.37–2.87). Safety: While VEN + DEC was associated with increased febrile neutropenia (OR = 1.99; 95% CI: 1.18–3.35), no significant increases were seen in anemia, leukopenia, or pneumonia, confirming a manageable toxicity profile. Conclusion: This meta-analysis provides compelling evidence that VEN + DEC significantly improves remission and survival outcomes in elderly AML patients, with an acceptable safety margin. The VEN 400 mg + DEC regimen appears to offer the most pronounced clinical benefit. These findings support VEN + DEC as a front-line therapeutic option and call for further prospective trials to optimize patient selection and treatment duration