Venetoclax, azacitidine, and chidamide in combination with cytarabine, aclarubicin, and G-CSF as induction chemotherapy for myelodysplasia-related acute myeloid leukemia.

Abstract

Myelodysplasia-related acute myeloid leukemia (AML-MR) exhibits poor outcomes with intensive chemotherapy. This retrospective study was conducted to evaluate the clinical efficacy and safety of the Venetoclax, Azacitidine, and Chidamide in combination with Cytarabine, Aclarubicin, and G-CSF (CACAG-VEN) regimen in AML-MR patients. We included 14-75-year-old AML-MR patients (n = 30) treated with CACAG-VEN between January 1, 2023 and December 31, 2024. And compared this cohort with patients (n = 30) who received the standard "3 + 7" regimen (daunorubicin plus cytarabine) from January 1, 2018 to December 31, 2022. The primary endpoint was the complete remission rate(CR) after one cycle of induction. In this retrospective analysis of 30 patients treated with CACAG-VEN, the median age was 50.5 (range, 23-62) years. The CACAG-VEN achieved a high CR (83.3%, 95% CI, 66.4-92.7) and composite complete response (CRc, 93.1% [95% CI, 78.7-98.8]). The 1-year overall survival (OS) and relapse incidences (CIR) were 90.0% (95% CI: 72.1-96.7) and 18.0% (95% CI: 6.4-34.4), respectively. No significant differences in OS (1-year: 85.7% [non-HSCT] vs. 93.8% [HSCT]) or CIR (1-year: 29.3% [non-HSCT] vs. 7.1% [HSCT]) were observed, regardless of whether patients underwent HSCT. The most frequent grade 1-4 adverse events were febrile neutropenia (73.3%), sepsis (16.7%), and pneumonia (50.0%). The median time to recovery was 16.5 days for platelet counts ≥ 20,000/µL and 20.0 days for absolute neutrophil counts ≥ 1,000 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: 55.7%, p = 0.003; CRc: 56.4%, p = 0.005; 1-year OS: 73.3%, p = 0.039). The CACAG-VEN regimen is a potential frontline therapy for AML-MR, yielding superior response rates and longer survival durations than the standard "3 + 7" chemotherapy.