Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy

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

doi:10.1093/jjco/hyab170

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy

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 ZhouJiuhong Zha, Jalaja Potluri, Itaru Matsumura

Leukemia

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Pages (from-to)	29-38
Number of pages	10
Journal	Japanese journal of clinical oncology
Volume	52
Issue number	1
DOIs	https://doi.org/10.1093/jjco/hyab170
State	Published - Jan 1 2022

Keywords

Japan
VIALE-A
acute myeloid leukemia
azacitidine
venetoclax

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

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10.1093/jjco/hyab170

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Yamamoto, K., Shinagawa, A., Dinardo, C. D., Pratz, K. W., Ishizawa, K., Miyamoto, T., Komatsu, N., Nakashima, Y., Yoshida, C., Fukuhara, N., Usuki, K., Yamauchi, T., Asada, N., Asou, N., Choi, I., Miyazaki, Y., Honda, H., Okubo, S., Kurokawa, M., ... Matsumura, I. (2022). Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Japanese journal of clinical oncology, 52(1), 29-38. https://doi.org/10.1093/jjco/hyab170

Yamamoto, K, Shinagawa, A, Dinardo, CD, Pratz, KW, Ishizawa, K, Miyamoto, T, Komatsu, N, Nakashima, Y, Yoshida, C, Fukuhara, N, Usuki, K, Yamauchi, T, Asada, N, Asou, N, Choi, I, Miyazaki, Y, Honda, H, Okubo, S, Kurokawa, M, Zhou, Y, Zha, J, Potluri, J & Matsumura, I 2022, 'Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy', Japanese journal of clinical oncology, vol. 52, no. 1, pp. 29-38. https://doi.org/10.1093/jjco/hyab170

@article{3ac5ab060f574263930c72454d5772fb,

title = "Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy",

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 = "Japan, VIALE-A, acute myeloid leukemia, azacitidine, venetoclax",

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

year = "2022",

month = jan,

day = "1",

doi = "10.1093/jjco/hyab170",

language = "English (US)",

volume = "52",

pages = "29--38",

journal = "Japanese journal of clinical oncology",

issn = "0368-2811",

publisher = "Oxford University Press",

number = "1",

}

TY - JOUR

T1 - Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy

AU - Yamamoto, Kazuhito

AU - Shinagawa, Atsushi

AU - Dinardo, Courtney D.

AU - Pratz, Keith W.

AU - Ishizawa, Kenichi

AU - Miyamoto, Toshihiro

AU - Komatsu, Norio

AU - Nakashima, Yasuhiro

AU - Yoshida, Chikashi

AU - Fukuhara, Noriko

AU - Usuki, Kensuke

AU - Yamauchi, Takahiro

AU - Asada, Noboru

AU - Asou, Norio

AU - Choi, Ilseung

AU - Miyazaki, Yasushi

AU - Honda, Hideyuki

AU - Okubo, Sumiko

AU - Kurokawa, Misaki

AU - Zhou, Ying

AU - Zha, Jiuhong

AU - Potluri, Jalaja

AU - Matsumura, Itaru

PY - 2022/1/1

Y1 - 2022/1/1

N2 - 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.

AB - 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.

KW - Japan

KW - VIALE-A

KW - acute myeloid leukemia

KW - azacitidine

KW - venetoclax

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U2 - 10.1093/jjco/hyab170

DO - 10.1093/jjco/hyab170

M3 - Article

C2 - 34739075

AN - SCOPUS:85123227995

SN - 0368-2811

VL - 52

SP - 29

EP - 38

JO - Japanese journal of clinical oncology

JF - Japanese journal of clinical oncology

IS - 1

ER -

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy

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