Patients with European LeukemiaNet (ELN) 2022 adverse-risk acute myeloid leukemia have poor prognoses with standard therapy. This study evaluated the novel venetoclax-azacitidine-chidamide plus CAG (CACAG-VEN) regimen in this population. In this retrospective analysis, we assessed 32 adverse-risk AML between January 1, 2023 and December 31, 2024, treated with the CACAG-VEN regimen (aclarubicin, azacitidine, cytarabine, chidamide, venetoclax plus G-CSF). Outcomes were analyzed relative to a historical cohort of 29 patients who received the standard “3 + 7” regimen between January 1, 2018 and December 31, 2022. The primary endpoint was the complete remission rate (CR) after one induction cycle. In this retrospective analysis of 32 patients treated with CACAG-VEN, the median age was 50.0 (range, 23–62) years. The CACAG-VEN achieved a high CR (87.5%, 95% CI, 71.9–95.0) and composite complete response (CRc, 93.8% 95% CI, 79.9–98.9). The 1-year overall survival and relapse incidences were 93.8% (95% CI: 77.3–98.4) and 16.7% (95% CI: 5.9–32.1), respectively. No significant differences in OS (1-year: 91.7% non-HSCT vs. 95.0% HSCT) or CIR (1-year: 25.0% non-HSCT vs. 11.1% HSCT) were observed, regardless of whether patients underwent HSCT. The most frequent grade 1–4 adverse events were febrile neutropenia (75.0%), pneumonia (53.1%), fatigue (13/32, 40.6%). The median time to recovery was 16.5 days for platelet counts ≥ 20,000/µL and 20.0 days for absolute neutrophil counts ≥ 500 cells/µL after induction therapy. The outcomes in the “3 + 7” group were inferior to those of patients who received the CACAG-VEN regimen (CR: 51.7%, p = 0.004; CRc: 55.2%, p < 0.001 ; 1-year OS: 51.7%, p < 0.001 ). The CACAG-VEN regimen demonstrates promising efficacy with a manageable safety profile as first-line therapy for adverse-risk AML, supporting its potential role in improving outcomes for this adverse-risk patient population.
Lv et al. (2026) studied this question.