Venetoclax with decitabine vs intensive chemotherapy in acute myeloid leukemia: A propensity score matched analysis stratified by risk of treatment‐related mortality

Abstract Hypomethylating agents (HMA) with venetoclax is a new standard for older/unfit patients with acute myeloid leukemia (AML). However, it is unknown how HMA with venetoclax compare to intensive chemotherapy (IC) in patients who are “fit” or “unfit” for IC. We compared outcomes of older patients with newly diagnosed AML receiving 10‐day decitabine with venetoclax (DEC10‐VEN) vs IC. DEC10‐VEN consisted of daily venetoclax with decitabine 20 mg/m 2 for 10 days for induction and decitabine for 5 days as consolidation. The IC cohort received regimens containing cytarabine ≥1 g/m 2 /d. A validated treatment‐related mortality score (TRMS) was used to classify patients at high‐risk or low‐risk for TRM with IC. Propensity scores were used to match patients to minimize bias. Median age of the DEC10‐VEN cohort (n = 85) was 72 years (range 63‐89) and 28% patients were at high‐risk of TRM with IC. The comparator IC group (n = 85) matched closely in terms of baseline characteristics. DEC10‐VEN was associated with significantly higher CR/CRi compared to IC (81% vs 52%, P < .001), and lower rate of relapse (34% vs 56%, P = .01), 30‐day mortality (1% vs 24%, P < .01), and longer overall survival (OS; 12.4 vs 4.5 months, HR = 0.48, 95%CI 0.29‐0.79, P < .01). In patients at both at high‐risk and low‐risk of TRM, DEC10‐VEN showed significantly higher CR/CRi, lower 30‐day mortality, and longer OS compared to IC. Patients at both high‐risk and low‐risk of TRM had comparable outcomes with DEC10‐VEN. In conclusion, DEC10‐VEN offers better outcomes compared to intensive chemotherapy in older patients with newly diagnosed AML, particularly in those at high‐risk of TRM.