Efficacy of venetoclax and azacitidine based therapy in favorable-risk unfit acute myeloid leukemia: a real-world study

Venetoclax combined with azacitidine (VA) is a new standard of care for newly diagnosed patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. We retrospectively analyzed patients who were diagnosed with favorable-risk unfit AML and received VA-based induction regimen between October 2020 and December 2023 in our center. Among 70 patients, 14 had RUNX1::RUNX1T1, 11 had CBFb::MYH11, 14 had CEBPA bzip mutations and 31 had NPM1 mutations. The median age was 60 years (IQR 49–67) and the median follow-up was 18.0 months (IQR 10.9–26.1). The cumulative CR/CRi rate of VA-based induction regimen for all patients was 84.3% (59/70). The median induction course was 1 (range 1–2). The CR/CRi rate for RUNX1::RUNX1T1, CBFb::MYH11, CEBPA bzip and NPM1 mutations was 35.7% (5/14), 90.9% (10/11), 100% (14/14) and 96.8% (30/31), respectively. Twenty patients received long-term VA-based therapy, and 30 received chemotherapy after remission. The MRD negativity rate after two cycle of consolidation therapy was 85.0% (17/20) for VA group and 73.3% (23/30) for chemotherapy group (p = 0.33). There was no significant difference in 2-year OS (p = 0.90) and 2-year EFS (p = 0.58) between VA group (OS: 88.2%; EFS: 41.2%) and chemotherapy group (OS: 83.3%; EFS: 42.8%). The 2-year OS (p = 0.01) and 2-year EFS (p < 0.01) of patients with negative MRD (OS: 89.8%; EFS: 51.4%) were significantly better than those with positive MRD (OS: 65.6%; EFS: 0%). VA-based regimens was an superior option for induction in favorable-risk unfit AML patients who were non-RUNX1::RUNX1T1 positive. Further studies are needed to conform its long-term efficacy.