Venetoclax Plus Azacitidine in Japanese Patients With Untreated Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy

Authors

Kazuhito Yamamoto
Atsushi Shinagawa
Courtney D DiNardo
Keith W Pratz
Kenichi Ishizawa
Toshihiro Miyamoto
Norio Komatsu
Yasuhiro Nakashima
Chikashi Yoshida
Noriko Fukuhara
Kensuke Usuki
Takahiro Yamauchi
Noboru Asada
Norio Asou
Ilseung Choi
Yasushi Miyazaki
Hideyuki Honda
Sumiko Okubo
Misaki Kurokawa
Ying Zhou
Jiuhong Zha
Jalaja Potluri
Itaru Matsumura

Publication Date

1-3-2022

Journal

Japanese Journal of Clinical Oncology

DOI

10.1093/jjco/hyab170

PMID

34739075

PMCID

PMC9242001

PubMedCentral® Posted Date

11-5-2021

PubMedCentral® Full Text Version

Post-print

Abstract

Background: The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.

Methods: Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1-7 of each 28-day cycle.

Results: Median follow-up was 16.3 months (range, 1.0-20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation.

Conclusions: This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.

Keywords

Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Bridged Bicyclo Compounds, Heterocyclic, Humans, Japan, Leukemia, Myeloid, Acute, Sulfonamides, acute myeloid leukemia, venetoclax, azacitidine, VIALE-A, Japan

Comments

This article has been corrected. See Jpn J Clin Oncol. 2023 Mar 24;53(5):456.

Published Open-Access

yes

Recommended Citation

Yamamoto, Kazuhito; Shinagawa, Atsushi; DiNardo, Courtney D; et al., "Venetoclax Plus Azacitidine in Japanese Patients With Untreated Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy" (2022). Faculty, Staff and Student Publications. 2991.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/2991