To investigate the clinical efficacy and safety of venetoclax tablet combined with azacitidine for injection in the treatment of newly diagnosed acute myeloid leukemia (AML) patients unsuitable for intensive chemotherapy.

Newly diagnosed AML patients unsuitable for intensive chemotherapy were divided into control group and treatment group based on treatment regimen. The control group received 75 mg·m^-2 azacitidine for injection by subcutaneous injection or intravenous infusion for 7 consecutive days per 28-day cycle. The treatment group received oral venetoclax tablet (dose escalation: 100 mg on day 1, 200 mg on day 2, and 400 mg daily from day 3 onwards) plus 75 mg·m^-2 azacitidine for injection, by subcutaneous injection or intravenous infusion for 7 consecutive days per 28-day cycle. Both groups were treated for 2 cycles. Clinical efficacy, hematological parameters [hemoglobin (Hb), platelet count (PLT), absolute neutrophil count (ANC), white blood cell count (WBC)], bone marrow morphology and cytogenetic assessments (proportion of bone marrow blasts, bone marrow cellularity), liver function indices [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL)], renal function index [serum creatinine (SCr)], coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer], survival outcomes [overall survival (OS), event-free survival (EFS)], and safety indicators were compared between the two groups.

A total of 230 patients were enrolled with 112 in the control group and 118 in the treatment group. After treatment, the overall response rate (ORR) in the treatment group was 74.58% (88 cases/118 cases), significantly higher than the control group’s 53.57% (60 cases/112 cases). The complete remission (CR) rate in the treatment group was 49.15% (58 cases/118 cases), significantly higher than the control group’s 26.79% (30 cases/112 cases); both differences were statistically significant (P<0.05). After treatment, Hb levels of treatment group and control group were (94.85±18.67) and (85.51±17.84) g·L^-1, respectively; PLT counts were (125.51±35.24) ×10⁹·L^-1 and (78.22±29.77) ×10⁹·L^-1, respectively; ANC levels were (4.23±1.87) ×10⁹·L^-1 and (2.79±1.16) ×10⁹·L^-1, respectively; WBC levels were (5.89±2.72) ×10⁹·L^-1 and (6.85±2.73) ×10⁹·L^-1, respectively;. the proportion of bone marrow blasts were (16.90±8.98)% and (29.16±14.18)%, respectively; the proportion of patients with active bone marrow hyperplasia were 80.51% (95 cases/118 cases) and 69.64% (78 cases/112 cases), respectively;. ALT levels were (58.56±25.14) and (45.78±16.57) U·L^-1, respectively; AST levels were (52.34±17.07) and (41.12±17.31) U·L^-1, respectively; TBIL levels were (31.65±12.10) and (25.33±9.12) μmol·L^-1, respectively; SCr levels were (84.32±19.19) and (82.13±17.55) μmol·L^-1, respectively; PT were (14.12±2.42) and (13.78±2.29) s, respectively; APTT were (34.12±5.10) and (33.22±4.65) s, respectively; FIB were (3.56±0.97) and (3.53±0.81) g·L^-1, respectively; D-dimer levels were (0.58±0.22) and (0.52±0.21) mg·L^-1, respectively. Except SCr, PT, APTT, FIB and D-dimer levels, comparion of other indicators between two groups showed statistically significant differences (all P<0.05). The median OS of treatment group and control group were 34.0 and 21.0 months, respectively;, median EFS was 28.0 and 11.0 months. Both median OS and median EFS were significantly longer in the treatment group compared to the control group (both P<0.05). The adverse event (AE) incidence rate was 28.57% (32 cases /112 cases) in the control group and 32.20% (38 cases/118 cases) in the treatment group, with no statistically significant difference (P>0.05).

Venetoclax tablet combined with azacitidine for injection significantly improved the ORR, CR rate, survival outcomes (OS, EFS), hematological recovery, and reduced bone marrow leukemic burden in newly diagnosed AML patients unsuitable for intensive chemotherapy. Although associated with an increased risk of liver toxicity, the overall safety profile was manageable. This combination regimen demonstrates significant clinical value.