Objective  To investigate the efficacy and safety of venetoclax combined with azacitidine in elderly patients with newly diagnosed acute myeloid leukemia (AML).

  Methods  The clinical data of 27 elderly patients with newly diagnosed AML who received venetoclax combined with azacitidine in The Second Affiliated Hospital of Air Force Military Medical University from September 2020 to December 2021, were retrospectively analyzed. The incidence of complete remission (CR)/CR with incomplete hematological recovery (CRi) rate, overall response rate (ORR), and minimal residual disease (MRD) status were monitored, and the factors of efficacy and prognosis and safety of the treatment protocol were analyzed.

  Results  The median number of treatment cycles administered was 3 (range, 1-9), CR/CRi rate was 51.9% (14/27), and ORR was 63.0% (17/27). After the initial treatment cycle, 44.4% of the patients achieved CR/CRi. Among all 14 patients with CR/CRi patients, 9 (64.3%) patients achieved MRD negativity after one or two treatment cycles. The response rate was higher in patients aged ≥70 years (P=0.035), hemoglobin (Hgb) count at diagnosis was ≥80 g/L (P=0.028), ASXL1 mutation (P=0.015), and no TP53 mutation (P=0.039). After the median follow-up time of 10.8（0.9–29.6）months, the median OS time of all the patients was unattained, and 1-year OS rate was 55.4%. In the univariate analysis, the proportion of bone marrow primordial cells upon diagnos is was ≥50% (P=0.015), with TP53 mutation (P<0.001) and without CR/CRi (P<0.001) were associated with poor OS, and multivariate analysis showed that the risk factors were also independent prognostic factors for OS (P<0.05). All patients manifested grade 3-4 hematological adverse reactions mainly in the initial course of treatment. Nonhematological adverse reactions were mainly pulmonary infections. Most patients could tolerate the nonhematological adverse reactions, and only one patient died early due to severe pulmonary infection.

  Conclusions  Venetoclax combined with azacitidine regimen in elderly patients with newly diagnosed AML is safe and effective. The age, Hgb count at diagnosis, ASXL1 mutation, and TP53 mutation are predictive factors for the response, and the proportion of bone marrow primordial cells upon diagnosis, TP53 mutation, and CR/CRi status are independent prognostic factors for OS.