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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

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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.

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Acknowledgments

This study was supported by Novartis Pharmaceuticals. Financial support for editorial assistance was provided by Novartis Pharmaceuticals. We thank Drs. Stacey Tobin, Clinton Lai and Nicholas D. Smith for providing editorial support.

Conflict of interest

Taro Amagasaki and Aira Wanajo are employees of Novartis Pharmaceuticals. The other authors have no conflicts of interest to disclose.

Author information

Author notes

  1. Yasuhiro Maeda

    Present address: National Hospital Organization Osaka Minami Medical Center, Osaka, Japan

  2. Hideo Tanaka

    Present address: Hiroshima City Asa Hospital, Hiroshima, Japan

Authors and Affiliations

  1. Division of Hematology, NTT Kanto Medical Center, 5-9-22 Higashigotanda, Shinagawa-ku, Tokyo, Japan

    Kensuke Usuki

  2. The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Arinobu Tojo

  3. Kinki University School of Medicine, Osaka, Japan

    Yasuhiro Maeda

  4. National Cancer Center Hospital, Tokyo, Japan

    Yukio Kobayashi

  5. International Medical Center, Saitama Medical University, Saitama, Japan

    Akira Matsuda

  6. Tokyo Medical University Hospital, Tokyo, Japan

    Kazuma Ohyashiki

  7. Chiba University Hospital, Chiba, Japan

    Chiaki Nakaseko

  8. Kumamoto University Hospital, Kumamoto, Japan

    Tatsuya Kawaguchi

  9. Hiroshima University Hospital, Hiroshima, Japan

    Hideo Tanaka

  10. Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Koichi Miyamura

  11. Nagasaki University Hospital, Nagasaki, Japan

    Yasushi Miyazaki

  12. Keio University Hospital, Tokyo, Japan

    Shinichiro Okamoto

  13. Osaka University Hospital, Osaka, Japan

    Kenji Oritani

  14. Hyogo College of Medicine, Hyogo, Japan

    Masaya Okada

  15. The Jikei University Daisan Hospital, Tokyo, Japan

    Noriko Usui

  16. Jichi Medical University Hospital, Tochigi, Japan

    Tadashi Nagai

  17. Novartis Pharma Japan, Tokyo, Japan

    Taro Amagasaki & Aira Wanajo

  18. Nagoya University Hospital, Nagoya, Japan

    Tomoki Naoe

Authors
  1. Kensuke Usuki
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  2. Arinobu Tojo
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  10. Koichi Miyamura
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  11. Yasushi Miyazaki
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  14. Masaya Okada
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  15. Noriko Usui
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  16. Tadashi Nagai
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  17. Taro Amagasaki
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  18. Aira Wanajo
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  19. Tomoki Naoe
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Corresponding author

Correspondence to Kensuke Usuki.

Additional information

This trial is registered at http://www.clinicaltrials.gov, number NCT01279473.

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Usuki, K., Tojo, A., Maeda, Y. et al. 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. Int J Hematol 95, 409–419 (2012). https://doi.org/10.1007/s12185-012-1026-9

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  • DOI: https://doi.org/10.1007/s12185-012-1026-9

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