Shortened Venetoclax Duration Based on Day 14 BM Blasts Versus Standard Therapy in Elderly or Frail Patients With AML Patients Treated With Azacitidine Plus Venetoclax

Prior treatment

• Prior treatment with venetoclax before the diagnosis of acute myeloid leukemia.
• Presence of active autoimmune diseases requiring treatment with prednisone ≥ 15 mg/day or equivalent doses of other glucocorticoids, or any other immunosuppressive agents.

Other illness

• A history of allogeneic hematopoietic stem cell transplantation.
• Presence of acute active infection requiring intravenous systemic therapy.
• Presence of active malignant tumors requiring antineoplastic treatment.
• Inability to swallow tablets, or presence of diseases significantly impairing gastrointestinal function (e.g., malabsorption syndrome, gastrectomy or enterectomy, bariatric surgery, symptomatic inflammatory bowel disease, or partial/complete intestinal obstruction).
• Subjects judged by the investigator to be unable to comply with the protocol due to uncontrollable medical, psychological, familial, social, or geographic conditions; or those who are unwilling or unable to follow the required procedures of the protocol.

Lab values

• Severe hepatic or renal impairment, defined by the presence of any of the following abnormalities: aspartate aminotransferase (AST) \> 2.5 × ULN; alanine aminotransferase (ALT) \> 2.5 × ULN; creatinine clearance rate \< 30 mL/min (calculated by the Cockcroft-Gault formula); or total bilirubin \> 3 × ULN.

Other

• Diagnosis of acute promyelocytic leukemia, AML with t(8;21)(q22;q22.1)/ RUNX1::RUNX1T1 translocation, or blast crisis of chronic myeloid leukemia (CML).
• Pregnant or lactating female subjects.

• Patients with newly diagnosed acute myeloid leukemia who meet the WHO 2022 criteria.
• Meeting one of the following conditions:
  • Aged ≥ 60 years;
  • aged ≥ 18 years and \< 60 years, with one or more of the following comorbidities that render the subject unsuitable for intensive induction therapy:
  • Complicated with congestive heart failure, or left ventricular ejection fraction ≤ 50%, or a history of chronic stable angina pectoris;
  • A history of pulmonary disease, with carbon monoxide diffusing capacity of the lung (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%;
  • Creatinine clearance rate \< 45 mL/min (calculated by the \*\*Cockcroft-Gault formula\*\*);
  • Total bilirubin \> 1.5 × upper limit of normal;
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥ 2;
  • Any other comorbidities judged by the investigator to contraindicate intensive induction therapy.
• Received induction therapy with the azacitidine plus venetoclax regimen (azacitidine for injection: 75 mg/m² subcutaneously on Days 1-7; venetoclax tablets: 100 mg on Day 1, 200 mg on Day 2, and 400 mg once daily starting on Day 3) for 12-14 days. Dose adjustment of venetoclax shall be performed if combined with strong or moderate CYP3A/P-gp inhibitors.
• Completed risk stratification assessment per the ELN 2022 criteria.
• Signed the informed consent form.