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International Journal of Hematology

, Volume 107, Issue 5, pp 535–540 | Cite as

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)

  • Jun Ishikawa
  • Itaru Matsumura
  • Tatsuya Kawaguchi
  • Junya Kuroda
  • Hirohisa Nakamae
  • Toshihiro Miyamoto
  • Ken-ichi Matsuoka
  • Hirohiko Shibayama
  • Masayuki Hino
  • Chikara Hirase
  • Tomohiko Kamimura
  • Takayuki Shimose
  • Koichi Akashi
  • Yuzuru Kanakura
Original Article
  • 462 Downloads

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.

Keywords

Chronic myelogeneous leukemia Deep molecular response Major molecular response Imatinib Nilotinib 

Notes

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.

Compliance with ethical standards

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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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Jun Ishikawa
    • 1
  • Itaru Matsumura
    • 2
  • Tatsuya Kawaguchi
    • 3
  • Junya Kuroda
    • 4
  • Hirohisa Nakamae
    • 5
  • Toshihiro Miyamoto
    • 6
  • Ken-ichi Matsuoka
    • 7
  • Hirohiko Shibayama
    • 8
  • Masayuki Hino
    • 5
  • Chikara Hirase
    • 2
  • Tomohiko Kamimura
    • 9
  • Takayuki Shimose
    • 10
  • Koichi Akashi
    • 6
  • Yuzuru Kanakura
    • 8
  1. 1.Department of HematologyOsaka International Cancer InstituteOsakaJapan
  2. 2.Department of Hematology and Rheumatology, Faculty of MedicineKindai UniversityOsakaJapan
  3. 3.Department of Hematology and Infectious DiseasesKumamoto UniversityKumamotoJapan
  4. 4.Division of Hematology and Oncology, Graduate School of MedicineKyoto Prefectural University of MedicineKyotoJapan
  5. 5.Department of Hematology, Graduate School of MedicineOsaka City UniversityOsakaJapan
  6. 6.Department of Medicine and Biosystemic Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  7. 7.Department of Hematology and OncologyOkayama UniversityOkayamaJapan
  8. 8.Department of Hematology and OncologyOsaka University Graduate School of MedicineOsakaJapan
  9. 9.Department of HematologyHarasanshin HospitalFukuokaJapan
  10. 10.Clinical Research Support Center KyushuFukuokaJapan

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