Impact of Venetoclax and Azacitidine in Treatment-Naive Patients with Acute Myeloid Leukemia and IDH1/2 Mutations

• Type of Material: Article
• Authors: Daniel A Pollyea, University of Colorado; Courtney D DiNardo, The University of Texas MD Anderson Cancer Center; Martha Arellano, Emory University; Arnaud Pigneux, CHU Bordeaux; Walter Fiedler, University Medical Center Hamburg-Eppendorf; Marina Konopleva, The University of Texas MD Anderson Cancer Center; David A Rizzieri, Novant Health Cancer Institute, Charlotte; Douglas B Smith, Johns Hopkins Medicine; Atsushi Shinagawa, Hitachi General Hospital; Roberto M Lemoli, University of Genoa; Monique Dail, Genentech Inc; Yinghui Duan, AbbVie Inc; Brenda Chyla, AbbVie Inc; Jalaja Potluri, AbbVie Inc; Catherine L Miller, AbbVie Inc; Hagop M Kantarjian, The University of Texas MD Anderson Cancer Center
• Language: English
• Date: 2022-07-01
• Publisher: AMER ASSOC CANCER RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: ©2022 The Authors; Published by the American Association for Cancer Research
• Final Published Version (URL): http://dx.doi.org/10.1158/1078-0432.CCR-21-3467
• Title of Journal or Parent Work: CLINICAL CANCER RESEARCH
• Volume: 28
• Issue: 13
• Start Page: 2753
• End Page: 2761
• Keywords: Oncology; PROGNOSTIC-SIGNIFICANCE; IVOSIDENIB; Science & Technology; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naive patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML). Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/ 11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group. Conclusions: Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.