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2886 Outcomes in Chemotherapy-Ineligible Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Venetoclax Plus Azacitidine: A Pooled Analysis

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, elderly, Diseases, Myeloid Malignancies, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Adriano Venditti, MD1, Jing-Zhou Hou2, Pierre Fenaux, MD, PhD3, Brian A. Jonas, MD, PhD4, Radovan Vrhovac5*, Pau Montesinos, PhD, MD6*, Jacqueline S. Garcia, MD7, David Rizzieri8*, Michael Thirman9, Stanley Kotey10*, Jalaja Potluri11, Mazaher Dhalla10* and Vinod Pullarkat, MD12

1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
2Hematology and BMT, Lemieux Center for Blood Cancers, UPMC Hillman Cancer Center, Pittsburgh, PA
3Department of Hematology, Université de Paris, Saint-Louis Hospital, Paris, France
4Department of Internal Medicine, Division of Malignant Hematology, Cellular Therapy and Transplantation, University of California Davis School of Medicine, Sacramento, CA
5Department of Haematology, University Hospital Centre Zagreb, and University of Zagreb School of Medicine, Zagreb, Croatia
6Hospital Universitari i Politecnic la Fe, Valencia, Spain
7Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
8Novant Health Cancer Institute, Winston Salem, NC
9Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
10AbbVie Inc., North Chicago, IL
11AbbVie Inc, North Chicago, IL
12Department of Hematology and Hematopoietic Cell Transplantation and Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, CA


Elderly patients (aged ≥75 years), with newly diagnosed acute myeloid leukemia (ND AML) frequently are ineligible to receive intensive chemotherapy (IC) and therefore have limited treatment options. The BCL-2 inhibitor venetoclax (Ven) in combination with azacitidine (Aza) was approved for the treatment of patients with ND AML who are ineligible for IC due to age or comorbidities based on the phase 3 VIALE-A trial. Treatment with Ven+Aza demonstrated rapid and durable remissions, with improved median overall survival (OS) versus placebo (Pbo)+Aza (14.7 vs 9.6 mo; hazard ratio [HR] 0.64) in patients enrolled in the VIALE-A trial (median age, 76 years). Although a subgroup analysis showed improvement in patients aged ≥75 years (HR 0.54; DiNardo C, et al. N Engl J Med. 2020;383:617), detailed analyses are lacking to further understand the impact of advanced patient age on the safety and efficacy of Ven+Aza. Here, we evaluate the outcomes of Ven+Aza across elderly age cohorts in patients with ND AML pooled from the open-label, single-arm, Phase 1b M14-358 trial of Ven plus hypomethylating agents in patients with ND AML who were ≥65 years old and IC-ineligible (NCT02203773) and the Phase 3 VIALE-A trial of Ven+Aza versus Pbo+Aza in patients with ND AML who were IC-ineligible (NCT02993523).


This analysis included IC-ineligible patients aged ≥75 years with ND AML pooled from the Ven+Aza arm of the M14-358 trial (NCT02203773) and the Ven+Aza and Pbo+Aza arms of the VIALE-A trial (NCT02993523). In both studies, patients received Ven daily (400 mg) with 75 mg/m2 subcutaneous (SC) or intravenous (IV) Aza on Days 1-7 of 28-day cycles). In VIALE-A, patients were randomized 2:1 to Ven+Aza or Pbo+Aza and received Ven (400 mg) or Pbo daily with Aza at the same schedule. For this post hoc analysis, patients were stratified by age (75–79 years, 80–84 years, and ≥85 years) to evaluate efficacy and safety, including complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate, minimal residual disease (MRD) response (<10-3) rate, OS, and Grade ≥3 treatment-emergent adverse events (TEAEs).


A total of 216 patients treated with Ven+Aza and 87 patients treated with Pbo+Aza were included, with n=120 and n=54 aged 75–79 years, n=75 and n=27 aged 80–84 years, and n=21 and n=6 aged ≥85 years (Table 1). Baseline disease characteristics were largely similar across age cohorts, including ECOG performance status and poor cytogenetic risk (Table 1). Baseline grade 3/4 neutropenia was more prevalent in patients aged ≥85 years.

Across the 75–79, 80–84, and ≥85 age cohorts, the CR/CRi rate was higher with Ven+Aza (67%, 68%, and 81%) vs Pbo+Aza (19%, 22%, and 17%) (Table 1). Ven+Aza also elicited a higher rate of MRD response (<10-3; 30%, 29%, and 29%) vs Pbo+Aza (13%, 11%, and 17%). Median OS (95% CI) was 14.1 mo (10.2–24.9) for those aged 75–79 years, 12.2 mo (8.0–21.8) for those aged 80–84 years, and 16.2 mo (9.3–20.5) for those aged ≥85 years in the Ven+Aza arm; in the Pbo+Aza arm, median OS (95% CI) was 8.5 mo (6.8–10.7), 10.1 mo (2.3–14.5), and 2.6 mo (0.2–not reached), respectively. In the Ven+Aza arm, median Ven dosing per cycle was 21 days across all age cohorts, with a median time from Day 1 of a cycle until Day 1 of the next cycle (including dose holds), of 31, 35, and 31 days for the 75–79, 80–84, and ≥85 age cohorts, respectively.

Rates of Grade ≥3 non-hematologic TEAEs were similar between age cohorts (Table 2). Consistent with the known safety profile of Ven+Aza, the most frequently reported hematologic TEAEs for the 75–79, 80–84, and ≥85 age cohorts included anemia (30%, 26%, and 48%), febrile neutropenia (43%, 38%, and 52%), neutropenia (34%, 37%, and 29%), and thrombocytopenia (36%, 48%, and 43%).


Ven+Aza led to higher rates of remission, including higher rates of MRD response, and longer median OS vs Pbo+Aza, while maintaining consistent safety data across all older patient cohorts (Table 1). Findings were consistent with data from the overall population in VIALE-A (median age of 76 years), emphasizing the benefit of Ven+Aza in the older population. Although the post hoc nature of the analysis and limited sample sizes require careful interpretation of differences between cohorts, these findings confirm Ven+Aza provides benefit across elderly patient cohorts with ND AML who are ineligible for IC.

Disclosures: Venditti: Medac: Consultancy; Janssen: Consultancy, Honoraria, Other: travel support ; AbbVie: Consultancy, Honoraria, Other: travel support ; Jazz: Consultancy, Honoraria, Other: travel support ; Amgen: Consultancy, Honoraria, Other: travel support ; Pfizer: Consultancy, Honoraria, Other: travel support , Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel support . Hou: AbbVie: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy. Fenaux: Janssen: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; French MDS Group: Honoraria. Jonas: Genentech/Roche: Research Funding; Forty-Seven: Research Funding; Forma: Research Funding; F. Hoffmann-La Roche: Research Funding; Celgene: Research Funding; Aptose: Research Funding; AROG: Research Funding; Amgen: Research Funding; Takeda: Consultancy; Servier: Consultancy; Rigel: Consultancy, Other: travel reimbursement ; Pfizer: Consultancy, Research Funding; Kymera: Consultancy; Jazz: Consultancy, Research Funding; GlycoMimetics: Consultancy, Other: protocol steering committee , Research Funding; Gilead: Consultancy, Other: data monitoring committee , Research Funding; Genentech: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; BMS: Consultancy, Research Funding; AbbVie: Consultancy, Other: travel reimbursement , Research Funding; Hanmi: Research Funding; Immune-Onc: Research Funding; Incyte: Research Funding; Loxo: Research Funding; Pharmacyclics: Research Funding; Sigma Tau: Research Funding; Treadwell: Research Funding. Vrhovac: AbbVie: Honoraria, Speakers Bureau; Astellas: Honoraria, Speakers Bureau; MSD: Honoraria; Novartis: Honoraria; Pfizer: Honoraria, Speakers Bureau; Pharmas: Honoraria, Speakers Bureau; Servier: Honoraria; Teva: Honoraria. Montesinos: Celgene: Consultancy; NERVIANO: Consultancy; INCYTE: Consultancy; Janssen: Speakers Bureau; BEIGENE: Consultancy; GILEAD: Consultancy; Takeda: Consultancy, Research Funding; Astellas: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding; Ryvu: Consultancy; Kura oncology: Consultancy; Menarini-Stemline: Consultancy, Research Funding; Jazz pharma: Consultancy, Research Funding, Speakers Bureau; OTSUKA: Consultancy; Abbvie: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Other, Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Garcia: Prelude: Research Funding; Servier: Consultancy; New Wave: Research Funding; AbbVie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Gilead: Consultancy; Astellas: Consultancy; Bristol Myers Squibb: Consultancy; Pfizer: Research Funding; AstraZeneca: Research Funding. Rizzieri: AbbVie: Honoraria, Speakers Bureau. Thirman: Nurix: Research Funding; AbbVie: Honoraria; Merck: Research Funding; Syndax: Research Funding; AbbVie: Research Funding. Kotey: AbbVie: Current Employment, Current holder of stock options in a privately-held company. Potluri: AbbVie: Current Employment, Current holder of stock options in a privately-held company. Dhalla: AbbVie: Current Employment, Current holder of stock options in a privately-held company. Pullarkat: Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau.

*signifies non-member of ASH