International Journal of Hematology

, Volume 110, Issue 6, pp 675–682 | Cite as

Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years: a multicenter phase 2 trial, stop nilotinib (NILSt)

  • Koji NagafujiEmail author
  • Itaru Matsumura
  • Takayuki Shimose
  • Tatsuya Kawaguchi
  • Junya Kuroda
  • Hirohisa Nakamae
  • Toshihiro Miyamoto
  • Norimitsu Kadowaki
  • Jun Ishikawa
  • Yutaka Imamura
  • Hirohito Yamazaki
  • Koichi Akashi
  • Yuzuru Kanakura
Original Article


The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300–400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidation therapy with nilotinib; 90 patients maintained MR4.5 with consolidation therapy, and 87 proceeded to discontinuation of nilotinib. The treatment-free remission (TFR) (MR4.5) rate at both 1 and 3 years after discontinuation of nilotinib was the same, at 60.9% (90% CI 51.6–69.7). Among 34 patients with molecular relapse, nilotinib was resumed in 33 patients; all of them attained MR4.5. There was no significant association between molecular relapse and age, sex, Sokal score, previous interferon-α exposure, duration of tyrosine kinase inhibitors treatment, or trough concentration of nilotinib. With nilotinib, it might be possible to avoid prognostic factors for TFR that exist with imatinib discontinuation. Cessation of nilotinib after two years of consolidation was safe and feasible.

Trial registration UMIN000007141.


Chronic myelogenous leukemia Tyrosine kinase inhibitor Nilotinib Discontinuation Cessation 



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

Author contributions

KN, IM, and NK contributed equally to the writing of the manuscript. IM, TK, JK, HN, and TM contributed equally to the study design. KN, NK, IJ, YI, and HY recruited the participating patients. TS carried out statistical analyses. KA and YK contributed equally to the organization of the study.

Compliance with ethical standards

Conflict of interest

KN, TS, JK, TM, JI, or YI have no competing financial interests. IM acts as a consultant to Otsuka, has received research funding from Bristol-Myers, and has received honoraria directly from Pfizer, Novartis Pharma KK, and Otsuka. HN acts as a consultant to Novartis Pharma KK, has received research funding from Novartis Pharma KK, has received honoraria directly from Novartis Pharma KK, and acts as Director of the Speakers Bureau, and is on advisory committees of Novartis Pharma KK. TK and HY have received honoraria directly from Novartis Pharma KK. NK has received research funding from Novartis Pharma KK and Pfizer, and has received honoraria directly from Novartis Pharma KK, Pfizer, and Bristol-Myers. KA has received research funding from Novartis Pharma KK. YK has received research funding from Pfizer and Bristol-Myers.


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Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  • Koji Nagafuji
    • 1
    Email author
  • Itaru Matsumura
    • 2
  • Takayuki Shimose
    • 3
  • Tatsuya Kawaguchi
    • 4
  • Junya Kuroda
    • 5
  • Hirohisa Nakamae
    • 6
  • Toshihiro Miyamoto
    • 7
  • Norimitsu Kadowaki
    • 8
  • Jun Ishikawa
    • 9
  • Yutaka Imamura
    • 10
  • Hirohito Yamazaki
    • 11
  • Koichi Akashi
    • 7
  • Yuzuru Kanakura
    • 12
  1. 1.Division of Hematology and Oncology, Department of MedicineKurume University School of MedicineKurumeJapan
  2. 2.Department of Hematology and RheumatologyKindai UniversityOsakaJapan
  3. 3.Clinical Research Support Center KyushuFukuokaJapan
  4. 4.Department of Hematology and Infectious DiseasesKumamoto UniversityKumamotoJapan
  5. 5.Division of Hematology and Oncology, Department of MedicineKyoto Prefectural University of MedicineKyotoJapan
  6. 6.Department of HematologyOsaka City UniversityOsakaJapan
  7. 7.Department of Medicine and Biosystemic ScienceKyushu UniversityFukuokaJapan
  8. 8.Department of Internal MedicineKagawa UniversityKagawaJapan
  9. 9.Department of Hematology and OncologyOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan
  10. 10.Division of HematologySt. Mary’s HospitalKurumeJapan
  11. 11.Division of Transfusion MedicineKanazawa University HospitalKanazawaJapan
  12. 12.Department of Hematology and OncologyOsaka UniversityOsakaJapan

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