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Nilotinib vs. imatinib in Japanese patients with newly diagnosed chronic myeloid leukemia in chronic phase: long-term follow-up of the Japanese subgroup of the randomized ENESTnd trial

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Abstract

In the ongoing, international, phase 3 study Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd), nilotinib 300 and nilotinib 400 mg, both twice daily, are compared with imatinib 400 mg once daily for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). Results for the overall population in ENESTnd (n = 846) showed that nilotinib resulted in higher response rates vs. imatinib and was well tolerated. Outcomes among Japanese patients in ENESTnd were specifically analyzed after 1 year of follow-up, and showed similar trends to the overall population; we present updated analysis of the Japanese subgroup based on 5 years of follow-up. Among Japanese patients in the nilotinib 300-mg (n = 29), nilotinib 400-mg (n = 23), and imatinib (n = 25) arms, 86.2, 78.3, and 60.0%, respectively, achieved major molecular response [BCR-ABL1 ≤ 0.1% on the International Scale (BCR-ABL1 IS)] by 5 years, and 65.5, 69.6, and 40.0%, respectively, achieved MR4.5 (BCR-ABL1 IS ≤ 0.0032%). Safety results were consistent with prior reports. In this subgroup, one death occurred during treatment in the nilotinib 400-mg twice-daily arm (unknown cause), and one patient in each arm progressed to accelerated phase/blast crisis by the data cutoff.

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Acknowledgements

Medical writing assistance for the preparation of this article was provided by Karen Kaluza, Ph.D. (ArticulateScience LLC) and funded by Novartis Pharma KK.

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Authors and Affiliations

  1. Hematology, Osaka City University Hospital, 1-5-7, Asahimachi, Abeno-ku, Osaka-shi, Osaka, 545-8586, Japan

    Hirohisa Nakamae

  2. Department of Hematology, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan

    Tetsuya Fukuda

  3. Department of Hematology, Chiba University Hospital, Chiba, Japan

    Chiaki Nakaseko

  4. Division of Hematology, Saitama Medical Center Jichi Medical University, Saitama, Japan

    Yoshinobu Kanda

  5. Division of Hematology, Jichi Medical University Hospital, Tochigi, Japan

    Ken Ohmine

  6. Oncology Center, Hamamatsu University Hospital, Shizuoka, Japan

    Takaaki Ono

  7. Department of Hematology, Kindai University Hospital, Osaka, Japan

    Itaru Matsumura

  8. Department of Hemato-Oncology, Saitama International Medical Center, Saitama Medical University, Saitama, Japan

    Akira Matsuda

  9. Novartis Pharma KK, Tokyo, Japan

    Makoto Aoki & Kazuo Ito

  10. Department of Hematology and Oncology, Osaka University Hospital, Osaka, Japan

    Hirohiko Shibayama

Authors
  1. Hirohisa Nakamae
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  2. Tetsuya Fukuda
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  3. Chiaki Nakaseko
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  4. Yoshinobu Kanda
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  5. Ken Ohmine
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  6. Takaaki Ono
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  7. Itaru Matsumura
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  8. Akira Matsuda
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  9. Makoto Aoki
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  10. Kazuo Ito
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  11. Hirohiko Shibayama
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Corresponding author

Correspondence to Hirohisa Nakamae.

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Conflict of interest

The authors declare the following relationships: Hirohisa Nakamae reports research funding from Novartis during the conduct of the study; consulting or advisory role, honoraria, and travel support from Novartis outside the submitted work; Tetsuya Fukuda reports honoraria from Novartis outside the submitted work; Chiaki Nakaseko reports research funding and honoraria from BMS and Pfizer outside the submitted work; honoraria from Novartis outside the submitted work; Yoshinobu Kanda reports personal fees from Novartis during the conduct of the study; personal fees from Dainippon-Sumitomo and Pfizer outside the submitted work; research funding and personal fees from Astellas, Kyowa-Hakko Kirin, Taisho-Toyama, and Merck Sharp & Dohme outside the submitted work; research funding from Chugai, Bristol-Myers Squibb, Takeda, Tanabe Mitsubishi, Toyama Kagaku, Nippon Shinyaku, Alexion, Yakult, Shionogi, Otsuka, and Nippon Kayaku outside the submitted work; Ken Ohmine reports personal fees Takara Bio Inc., Ono Pharmaceutical Co., Ltd., and Kyowa Kirin Pharmaceutical Development Inc. outside the submitted work; Takaaki Ono reports research funding from Celgene, Kyowa Hakko Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Toyama Kagaku, and Merck Sharp & Dohme outside the submitted work; Itaru Matsumura reports research funding and personal fees from Bristol-Myers Squibb and Pfizer Japan Inc. during the conduct of the study; personal fees from Novartis Pharma KK during the conduct of the study; Akira Matsuda reports study fees from Kyowa Hakko Kirin Co., Ltd. and GlaxoSmithKline during the conduct of the study; research grant from Chugai Pharmaceutical Co., Ltd. during the conduct of the study; personal fees from Nippon Shinyaku Co., Ltd., Alexion Pharmaceuticals, Inc., Sanofi KK, GlaxoSmithKline KK, Kyowa Hakko Kirin Co., Ltd., outside the submitted work; Makoto Aoki is employed by Novartis Pharma KK; Kazuo Ito is employed by Novartis Pharma KK; Hirohiko Shibayama reports research funding, consulting or advisory role, honoraria and lecture fees from Novartis during the conduct of the study.

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Nakamae, H., Fukuda, T., Nakaseko, C. et al. Nilotinib vs. imatinib in Japanese patients with newly diagnosed chronic myeloid leukemia in chronic phase: long-term follow-up of the Japanese subgroup of the randomized ENESTnd trial. Int J Hematol 107, 327–336 (2018). https://doi.org/10.1007/s12185-017-2353-7

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  • DOI: https://doi.org/10.1007/s12185-017-2353-7

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