Venetoclax Plus “3+7” Chemotherapy As the First-Line Therapy for Adult Patients With Acute Myeloid Leukemia

Background: Adult patients with acute myeloid leukemia (AML) have unsatisfactory complete remission (CR) and clinical outcomes. Venetoclax combined with azacytidine or low lose cytarabine has showed definite efficacy in elderly AML patients.Methods: We conducted a two-stage, phase 2 clinical trial to test whether venetoclax added to daunorubicin + cytarabine induction treatment could increase CR rate from 65% to more than 85% after one cycle of therapy. We enrolled 33 adult AML patients (18-60 years old). Induction treatment included daunorubicin (60 mg/m2, days 1-3), cytarabine (100 mg/m2, days 1-7) and venetoclax (100 mg day 4, 200 mg day 5, and 400 mg days 6-11) (DAV regimen). The primary endpoint was composite complete remission rate.Findings: The CR rate after one cycle of DAV regimen was 91% (95% confidence interval, 76 to 98) in 33 patients, and 100%, 83%, and 75% in ELN favorable, intermediate and poor-risk groups. 29 (97%) of 30 patients who achieved CR had undetectable measurable residual disease (MRD<0.1%). Grade 3 and 4 adverse events included neutropenia in 33 (100%), thrombocytopenia in 33 (100%), anemia in 33 (100%), febrile neutropenia in 28 (54%), pneumonia in 7 (21%), and sepsis in 4 (12%) patients. A rapid recovery of myelosuppression was found. With a median follow-up of 6 months, 30 patients were in continuous CR (29 with MRD-negative).Interpretation: DAV regimen represents an effective induction treatment for newly diagnosed adult AML patients, which was associated with high and deep remission, and rapid recovery of myelosuppression.Trial Registration Details: Clinical Trial Registry Number: ChiCTR2000041509. Funding Information: Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang, National Natural Science Foundation of China, key research and development program of Zhejiang. Declaration of Interests: All other authors declare no competing interests.Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of the First Affiliated Hospital of Zhejiang University School of Medicine. The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonization guidelines for Good Clinical Practice. All patients gave written informed consents prior to any procedure.