Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.

3rd Faculty of Medicine Charles University Prague Czech Republic

AbbVie Inc North Chicago IL; and

Almazov National Medical Research Center Saint Petersburg Russia

Centre Hospitalier Le Mans Le Mans France

Centre Intégré Universitaire de Santé et de Services Sociaux de l'Est de l'Île de Montréal Installation Maisonneuve Rosemont Montreal QC Canada

Centro de Investigación Biomedica en Red en Cancer Instituto Carlos 3 Madrid Spain

Department of Internal Medicine and Hematology University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Leukemia The University of Texas MD Anderson Cancer Center Houston TX

Evaggelismos General Hospital Athens Greece

George Papanicolaou General Hospital Thessaloniki Greece

Heartlands Hospital Birmingham United Kingdom

Hospital Universitario y Politecnico La Fe Valencia Spain

Hubertus Wald University Cancer Center University Medical Center Hamburg Eppendorf Hamburg Germany

Laiko General Hospital National and Kapodistrian University of Athens Medical School Athens Greece

Leukaemia Translational Research Central Clinical School Monash University Melbourne VIC Australia

Netcare Pretoria East Hospital Pretoria South Africa

Nizhny Novgorod Regional Clinical Hospital Nizhny Novgorod Russia

Norton Cancer Institute Louisville KY

Seoul National University Hospital Seoul South Korea

The Alfred Hospital Melbourne VIC Australia

Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

University of Fukui Hospital Fukui Japan

University of Pittsburgh Medical Center Cancer Center Pittsburgh PA

Blood. 2020 Jun 11;135(24):2114-2115. doi: 10.1182/blood.2020005651. PubMed

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ClinicalTrials.gov
NCT03069352