Enhanced Remission and Survival Outcomes with Decitabine Plus Venetoclax in Additional Sex Comb Like 1 Mutated Acute...

Decitabine (DEC) and Venetoclax (VEN) are approved for elderly adult acute myeloid leukemia (AML) patients with an additional sex comb-like 1 (ASXL1) mutation who cannot tolerate intensive chemotherapy. However, direct comparative data in this population remain limited. A systematic review and meta-analysis were conducted to assess the indirect efficacy of DEC alone and VEN in older AML patients with ASXL1 mutations. A matched cohort was created by comparing outcomes of consecutive adults with AML who received DEC or DEC with VEN after propensity score matching using the nearest-neighbor methodology. The DEC + VEN cohort had a lower early mortality rate than the DEC cohort (30-day mortality: 2.7%-5% vs. 9.7%, p = 0.01; RR = 0.90, 95% CI 0.83-0.97 versus RR = 0.97, 95% CI 0.92-1.02). However, the 30-day and 60-day mortality rates were similar between groups (9.5% vs. 2.7%, p = 0.17; 18.9% vs. 9.5%, p = 0.16). Overall survival (OS) was measured at 7.9-25.1 months. The DEC + VEN cohort had significantly higher response rates than the decitabine cohort. According to the 2017 EL N Genetic Risk classification, people with a favorable moderate risk had a higher rate of complete response or complete response with incomplete hematologic recovery than those with high risk (65% vs. 34%). The use of DEC for 5 or 10 days as the hypomethylating agents combination with VEN did not affect the CR/Cri rate. In conclusion, DEC plus VEN was associated with improved clinical responses and survival signals in ASXL1-mutated AML, warranting prospective confirmation.