International Journal of Hematology

, Volume 95, Issue 4, pp 409–419

Efficacy and safety of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL: a 36-month analysis of a phase I and II study

  • Kensuke Usuki
  • Arinobu Tojo
  • Yasuhiro Maeda
  • Yukio Kobayashi
  • Akira Matsuda
  • Kazuma Ohyashiki
  • Chiaki Nakaseko
  • Tatsuya Kawaguchi
  • Hideo Tanaka
  • Koichi Miyamura
  • Yasushi Miyazaki
  • Shinichiro Okamoto
  • Kenji Oritani
  • Masaya Okada
  • Noriko Usui
  • Tadashi Nagai
  • Taro Amagasaki
  • Aira Wanajo
  • Tomoki Naoe
Original Article

DOI: 10.1007/s12185-012-1026-9

Cite this article as:
Usuki, K., Tojo, A., Maeda, Y. et al. Int J Hematol (2012) 95: 409. doi:10.1007/s12185-012-1026-9

Abstract

Although the tyrosine kinase inhibitor (TKI) imatinib is often used as first-line therapy for newly diagnosed chronic myelogenous leukemia (CML), some patients fail to respond, or become intolerant to imatinib. Nilotinib is a potent and selective second-generation TKI, with confirmed efficacy and tolerability in patients with imatinib-resistant or -intolerant CML. A phase I/II study was conducted in Japanese patients with imatinib-resistant or -intolerant CML or relapsed/refractory Ph+ acute lymphoblastic leukemia. Thirty-four patients were treated with nilotinib for up to 36 months. Major cytogenetic response was achieved in 15/16 patients (93.8%) with chronic-phase CML within a median of approximately 3 months. Major molecular response was achieved in 13/16 patients (81.3%). These responses were sustained at the time of the most recent evaluation in 13 patients and 11 patients, respectively. Hematologic and cytogenetic responses were also observed in patients with advanced CML. The BCR-ABL mutation associated with the most resistance to available TKIs, T315I, was observed in three patients. Common adverse events included rash, nasopharyngitis, leukopenia, neutropenia, thrombocytopenia, nausea, headache and vomiting. Most adverse events resolved following nilotinib dose interruptions/reductions. These results support the favorable long-term efficacy and tolerability of nilotinib in Japanese patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia.

Keywords

Chronic myeloid leukemia Acute lymphoblastic leukemia Tyrosine kinase inhibitors Nilotinib 

Supplementary material

12185_2012_1026_MOESM1_ESM.doc (263 kb)
Supplementary material 1 (DOC 263 kb)

Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Kensuke Usuki
    • 1
  • Arinobu Tojo
    • 2
  • Yasuhiro Maeda
    • 3
    • 19
  • Yukio Kobayashi
    • 4
  • Akira Matsuda
    • 5
  • Kazuma Ohyashiki
    • 6
  • Chiaki Nakaseko
    • 7
  • Tatsuya Kawaguchi
    • 8
  • Hideo Tanaka
    • 9
    • 20
  • Koichi Miyamura
    • 10
  • Yasushi Miyazaki
    • 11
  • Shinichiro Okamoto
    • 12
  • Kenji Oritani
    • 13
  • Masaya Okada
    • 14
  • Noriko Usui
    • 15
  • Tadashi Nagai
    • 16
  • Taro Amagasaki
    • 17
  • Aira Wanajo
    • 17
  • Tomoki Naoe
    • 18
  1. 1.Division of HematologyNTT Kanto Medical CenterTokyoJapan
  2. 2.The Institute of Medical Science, The University of TokyoTokyoJapan
  3. 3.Kinki University School of MedicineOsakaJapan
  4. 4.National Cancer Center HospitalTokyoJapan
  5. 5.International Medical CenterSaitama Medical UniversitySaitamaJapan
  6. 6.Tokyo Medical University HospitalTokyoJapan
  7. 7.Chiba University HospitalChibaJapan
  8. 8.Kumamoto University HospitalKumamotoJapan
  9. 9.Hiroshima University HospitalHiroshimaJapan
  10. 10.Japanese Red Cross Nagoya First HospitalNagoyaJapan
  11. 11.Nagasaki University HospitalNagasakiJapan
  12. 12.Keio University HospitalTokyoJapan
  13. 13.Osaka University HospitalOsakaJapan
  14. 14.Hyogo College of MedicineHyogoJapan
  15. 15.The Jikei University Daisan HospitalTokyoJapan
  16. 16.Jichi Medical University HospitalTochigiJapan
  17. 17.Novartis Pharma JapanTokyoJapan
  18. 18.Nagoya University HospitalNagoyaJapan
  19. 19.National Hospital Organization Osaka Minami Medical CenterOsakaJapan
  20. 20.Hiroshima City Asa HospitalHiroshimaJapan

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