Venetoclax-azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE-A study (NCT02993523). Here, long-term follow-up is presented to address survival benefit and long-term outcomes with venetoclax-azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax-azacitidine or placebo-azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE-A, 431 patients were enrolled to venetoclax-azacitidine (n = 286) or placebo-azacitidine (n = 145). At 43.2 months median follow-up, median OS was 14.7 months (95% confidence interval [CI], 12.1-18.7) with venetoclax-azacitidine, and 9.6 months (95% CI, 7.4-12.7) with placebo-azacitidine (hazard ratio, 0.58 [95% CI, 0.47-0.72], p < .001); the estimated 24-month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any-grade hematologic and gastrointestinal adverse events were most common in venetoclax-azacitidine and placebo-azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long-term efficacy and safety confirm venetoclax-azacitidine is an improvement in standard-of-care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities.

AbbVie Inc North Chicago Illinois USA

Abramson Cancer Center University of Pennsylvania Philadelphia Pennsylvania USA

Aichi Cancer Center Nagoya Japan

Cancer Research Center of Toulouse Toulouse France

Centre Hospitalier Universitaire de Toulouse Institut Universitaire du Cancer de Toulouse Oncopole Toulouse France

Clinic of Hematology Department of Internal Medicine University of Genoa Genoa Italy

Dana Farber Cancer Institute Harvard Medical School Boston Massachusetts USA

Department of Hematology and Hematopoietic Cell transplantation and Gehr Family Center for Leukemia Research City of Hope Comprehensive Cancer Center Duarte California USA

Department of Hematology Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki Helsinki Finland

Department of Hematology Hospital Clinic August Pi i Sunyer Biomedical Research Institute Barcelona Spain

Department of Internal Medicine 3 Ulm University Hospital Ulm Germany

Department of Internal Medicine China Medical University Hospital Taichung Taiwan

Department of Internal Medicine Division of Malignant Hematology Cellular Therapy and Transplantation University of California Davis School of Medicine Sacramento California USA

Department of Internal Medicine Seoul National University College of Medicine Seoul South Korea

Department of Internal Medicine University Hospital Brno and Masaryk University Brno Czech Republic

Department of Leukemia Division of Cancer Medicine University of Texas MD Anderson Cancer Center Houston Texas USA

Department of Medicine McMaster University Hamilton Ontario Canada

Faculty of Medicine Department of Hematology University of Debrecen Debrecen Hungary

Faculty of Medicine Department of Internal Medicine Division of Hematology Ondokuz Mayis University Samsun Turkey

Genentech Inc South San Francisco California USA

Institute of Hematology and Hospital of Blood Disease Chinese Academy of Medical Sciences Peking Union Medical College Tianjin China

Institute of Hematology Davidoff Cancer Center Rabin Medical Center Petah Tikva and Tel Aviv University Tel Aviv Israel

IRCCS San Martino Hospital Genoa Genoa Italy

Section of Hematology and Oncology Department of Medicine University of Chicago Medicine Chicago Illinois USA

Université Toulouse 3 Paul Sabatier Toulouse France

University Medical Center Hamburg Eppendorf Hamburg Germany

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