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A phase II randomized study evaluating azacitidine versus conventional care regimens in newly diagnosed elderly Japanese patients with unfavorable acute myeloid leukemia

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Abstract

A multicenter phase II study was conducted in 44 elderly (≥ 65 years) Japanese patients with newly diagnosed acute myeloid leukemia (AML) to evaluate whether azacitidine is also effective and feasible in Japanese AML patients. The 28 patients with AML with poor-risk cytogenetics and/or myelodysplasia-related changes (unfavorable AML) were randomly assigned to receive either azacitidine or conventional care regimens (CCR), and the other 16 patients without unfavorable AML received azacitidine alone. The primary endpoint was overall survival. At the median follow-up of 29 months, among the 26 evaluable patients with unfavorable AML, the median survival time (MST) of patients who received azacitidine (N = 14) was 9.6 months and that of patients who received CCR (N = 12) was 5.3 months (HR 0.73; 95% CI 0.31–1.69; log-rank P = 0.459). The MST of all 29 patients who received azacytidine, including the 15 evaluable patients without unfavorable AML, was 12.4 months. Adverse events of azacitidine were manageable and consistent with its established safety profile. Azacitidine tended to prolong survival in newly diagnosed elderly Japanese patients with AML, and was feasible as a front-line therapy for elderly AML patients.

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Acknowledgements

This study was sponsored by Nippon Shinyaku Co., Ltd. The sponsors of the study were involved in the study design, data collection, statistical analysis, data interpretation, and medical writing. The authors wish to thank the study group, subinvestigators, study staff, and patients. The members of Study group: Kensuke Usuki, Department of Hematology, NTT Medical Center Tokyo. Kiyoshi Ando, Department of Hematology and Oncology, Tokai University School of Medicine. Takahiro Yamauchi, Department of Hematology and Oncology, University of Fukui. Junya Kuroda, Division of Hematology and Oncology, Kyoto Prefectural University of Medicine. Takayuki Ishikawa, Department of Hematology, Kobe City Medical Center General Hospital. Hiromi Iwasaki, Department of Hematology, National Hospital Organization Kyushu Medical Center. Takahiro Suzuki, Department of Hematology, Kitasato University School of Medicine. Kenichi Kitamura, Division of Hematology, Saiseikai Shiga Hospital. Hitoji Uchiyama, Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital. Satoshi Ichikawa, Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine. Kenji Imajo, Hematology and Oncology Center, Okayama City Hospital. Hitoshi Hanamoto, Department of Hematology, Kindai University Nara Hospital. Shuichi Miyawaki, Division of Hematology, Tokyo Metropolitan Ohtsuka Hospital. Noriko Usui, Department of Clinical Oncology and Hematology, The Jikei University School of Medicine. Norio Asou, Department of Hematology, International Medical Center, Saitama Medical University. Akihiro Hirakawa, Department of Clinical Biostatistics, Tokyo Medical and Dental University. Kazutaka Kuriyama, Division of Clinical Laboratory, Nagasaki Harbor Medical Center. Masakazu Muta, Department of Clinical Laboratory, National Hospital Organization Beppu Medical Center. Masafumi Taniwaki, Center for Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine. Yukari Takahashi, Clinical Development Dept., Nippon Shinyaku Co., Ltd. Atsushi Dohi, Clinical Development Dept., Nippon Shinyaku Co., Ltd. Yoko Nakanishi, R&D Administration Dept., Nippon Shinyaku Co., Ltd. Ryuhei Nakaoka, Data Science Dept., Nippon Shinyaku Co., Ltd.

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Authors and Affiliations

  1. Department of Hematology, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-ku, Nagoya, Aichi, Japan

    Hiroatsu Iida

  2. Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Osaka, Japan

    Kazunori Imada

  3. Department of Hematology/Oncology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan

    Yasunori Ueda

  4. Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Aomori, Japan

    Kohmei Kubo

  5. Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Chiba, Japan

    Akira Yokota

  6. Department of Hematology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan

    Yoshikazu Ito

  7. Department of Hematology, Chugoku Central Hospital, Fukuyama, Hiroshima, Japan

    Toru Kiguchi

  8. Department of Hematology, Nagasaki University Hospital, Nagasaki, Nagasaki, Japan

    Tomoko Hata

  9. Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan

    Yuichiro Nawa

  10. Department of Hematology, Fukushima Medical University, Fukushima, Fukushima, Japan

    Takayuki Ikezoe

  11. Department of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Aichi, Japan

    Toshiki Uchida

  12. Department of Hematology and Rheumatology, Kindai University School of Medicine, Osakasayama, Osaka, Japan

    Yasuyoshi Morita

  13. Department of Hematology and Oncology, University of Yamanashi, Chuo, Yamanashi, Japan

    Ichiro Kawashima

  14. Clinical Development Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan

    Masahiro Chiba & Shihomi Hirooka

  15. Data Science Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan

    Kensaku Morimoto

  16. Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Nagasaki, Japan

    Yasushi Miyazaki

  17. Aichi Cancer Center, Nagoya, Aichi, Japan

    Ryuzo Ohno

  18. National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan

    Tomoki Naoe

Authors
  1. Hiroatsu Iida
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  2. Kazunori Imada
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  3. Yasunori Ueda
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  5. Akira Yokota
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  6. Yoshikazu Ito
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  7. Toru Kiguchi
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  8. Tomoko Hata
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  14. Masahiro Chiba
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Consortia

the Study Group

  • Kensuke Usuki
  • , Kiyoshi Ando
  • , Takahiro Yamauchi
  • , Junya Kuroda
  • , Takayuki Ishikawa
  • , Hiromi Iwasaki
  • , Takahiro Suzuki
  • , Kenichi Kitamura
  • , Hitoji Uchiyama
  • , Satoshi Ichikawa
  • , Kenji Imajo
  • , Hitoshi Hanamoto
  • , Shuichi Miyawaki
  • , Noriko Usui
  • , Norio Asou
  • , Akihiro Hirakawa
  • , Kazutaka Kuriyama
  • , Masakazu Muta
  • , Masafumi Taniwaki
  • , Yukari Takahashi
  • , Atsushi Dohi
  • , Yoko Nakanishi
  •  & Ryuhei Nakaoka

Corresponding author

Correspondence to Hiroatsu Iida.

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Conflict of interest

Azacitidine was provided by Nippon Shinyaku Co., Ltd. IH reports all support for the present manuscript from Nippon Shinyaku Co., Ltd., grants from Chugai Pharmaceutical Co., Ltd., and payment from Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Janssen Pharmaceutical K.K., Novartis Pharma K.K., and Abbvie Inc. KI reports honoraria from Nippon Shinyaku Co., Ltd. AY reports payments from Nippon Shinyaku Co., Ltd. TK reports grants from Nippon Shinyaku Co., Ltd. TU reports honoraria from Pfizer Japan Inc. YM reports research funding of this study from Nippon Shinyaku Co., Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., and payments from Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd, Kyowa Kirin Co., Ltd., Abbvie Inc., Novartis Pharma K.K., Bristol-Myers-Squibb K.K., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Eisai Co., Ltd., Daiichi Sankyo Company Limited., Takeda Pharmaceutical Company Limited., Sanofi K.K. and Nippon Shinyaku Co., Ltd. TN reports grants from Astellas Pharma Inc., Daiichi Sankyo Company Limited. And FUJIFILM Corporation., payments from Astellas Pharma Inc., Bristol-Myers-Squibb K.K., Otsuka Pharmaceutical Co., Ltd., Sysmex Corporation and Nippon Shinyaku Co., Ltd. RO reports consulting fees from Nippon Shinyaku Co., Ltd.

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The members of the Study Group are listed in acknowledgements.

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Iida, H., Imada, K., Ueda, Y. et al. A phase II randomized study evaluating azacitidine versus conventional care regimens in newly diagnosed elderly Japanese patients with unfavorable acute myeloid leukemia. Int J Hematol 115, 694–703 (2022). https://doi.org/10.1007/s12185-022-03307-x

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  • DOI: https://doi.org/10.1007/s12185-022-03307-x

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