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Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib: results of a multicenter phase II trial (NILSw trial)

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Abstract

We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22–76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6%, (90% CI 38.2–66.7%)] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy.

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Acknowledgements

This study was supported and funded by Novartis Pharmaceutical Corporation. We would like to thank all of the participated patients and their families. We are indebted to the physicians, all other co-medical staff and Independent Data Monitoring Committee (Masahiro Kizaki, Kazuma Ohyashiki and Noriko Usui) who contributed to this study. We also thank the stuffs at the Clinical Research Support Center Kyushu (CReS Kyushu) for their excellent collection and management of data, secretarial assistance, and any other supports.

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Authors and Affiliations

  1. Department of Hematology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan

    Jun Ishikawa

  2. Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka, Japan

    Itaru Matsumura & Chikara Hirase

  3. Department of Hematology and Infectious Diseases, Kumamoto University, Kumamoto, Japan

    Tatsuya Kawaguchi

  4. Division of Hematology and Oncology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Junya Kuroda

  5. Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Hirohisa Nakamae & Masayuki Hino

  6. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toshihiro Miyamoto & Koichi Akashi

  7. Department of Hematology and Oncology, Okayama University, Okayama, Japan

    Ken-ichi Matsuoka

  8. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan

    Hirohiko Shibayama & Yuzuru Kanakura

  9. Department of Hematology, Harasanshin Hospital, Fukuoka, Japan

    Tomohiko Kamimura

  10. Clinical Research Support Center Kyushu, Fukuoka, Japan

    Takayuki Shimose

Authors
  1. Jun Ishikawa
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  2. Itaru Matsumura
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  3. Tatsuya Kawaguchi
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  4. Junya Kuroda
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  5. Hirohisa Nakamae
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  6. Toshihiro Miyamoto
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  7. Ken-ichi Matsuoka
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  8. Hirohiko Shibayama
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  9. Masayuki Hino
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  10. Chikara Hirase
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  11. Tomohiko Kamimura
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  12. Takayuki Shimose
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  13. Koichi Akashi
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  14. Yuzuru Kanakura
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Corresponding author

Correspondence to Jun Ishikawa.

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Conflict of interest

I. M. acted as a consultant for Otsuka and received honoraria for Otsuka, Novartis, Bristol-Myers Squibb. J. K. received research funding from Celgene, Bristol-Myers Squibb and Astra Zeneca and honoraria for Celgene, Bristol-Myers Squibb and Janssen. H. N. acted as a consultant and received research funding and honoraria from Novartis. H. S. received research funding and speaker bureau from Novartis. M. H. received research funding and honoraria from Novartis. K. A. acted as a consultant for Sumitomo Dainippon and Kyowa Hakko Kirin and received research funding from Celgene, Kyowa Hakko Kirin, Astellas, Shionogi, Asahi Kasei, Chugai, Bristol-Myers Squibb. Y. K. received research funding from Kyowa Hakko Kirin, Shionogi, Chugai, Pfizer, Eisai, Astellas, Nippon Shinyaku, Alexionpharma, Bristol-Myers Squibb, Toyama Chemical, Fujimotoseiyaku. The remaining authors declare no competing financial interests.

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Ishikawa, J., Matsumura, I., Kawaguchi, T. et al. Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib: results of a multicenter phase II trial (NILSw trial). Int J Hematol 107, 535–540 (2018). https://doi.org/10.1007/s12185-018-2401-y

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  • DOI: https://doi.org/10.1007/s12185-018-2401-y

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