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Clinical efficacy and safety of first-line nilotinib therapy and evaluation of the clinical utility of the FRET-based drug sensitivity test

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Abstract

Nilotinib is widely used for primary treatment of patients with chronic myelogenous leukemia (CML). We previously reported that use of an FRET-based drug sensitivity test at diagnosis efficiently predicts the response to treatment with imatinib or dasatinib. Here, we conducted a phase-II study to evaluate the efficacy and safety of nilotinib treatment and identify useful biomarkers, including results of the FRET-based drug sensitivity test, for predicting treatment response. Data from 42 patients were used in the analysis. Major molecular response (MMR), MR4, and MR4.5 rates at 12 months were 64.3, 42.9, and 28.6%, respectively. Grade 3/4 non-hematologic adverse events occurred in 11 patients (26.2%). The dose intensity of nilotinib (> 76.44%) and halving time (HT, < 13.312 days) were identified as significant factors for MMR at 12 months. However, when we focused on patients whose dose intensity of nilotinib was > 76.44%, the FRET-based drug sensitivity test became a predictive factor of MR4 achievement at 12 months. Our study reconfirmed the efficacy and safety of nilotinib treatment in CML patients. Moreover, our results suggest that the FRET-based drug sensitivity test is an independent predictor for achievement of MR4 in patients treated with a sufficient dose intensity of nilotinib.

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Acknowledgements

We thank Ms. Utako Hata of the Hokkaido University Hospital Clinical Research and Medical Innovation Center for data management and Novartis Pharma for providing nilotinib. This work was supported by JSPS KAKENHI Grant Number 25461404 (T.K.) and by a research fund from the North Japan Hematology Study Group.

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Authors and Affiliations

  1. Department of Hematology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Takeshi Kondo & Takanori Teshima

  2. Blood Disorders Center, Aiiku Hospital, S4W25, Chuo-ku, Sapporo, 064-0804, Japan

    Takeshi Kondo & Akio Mori

  3. Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Mari Fujioka & Yusuke Ohba

  4. Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan

    Shinichi Fujisawa & Kaori Sato

  5. Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Masumi Tsuda

  6. Department of Internal Medicine, Japan Labour Health and Welfare Organization, Kushiro Rosai Hospital, Kushiro, Japan

    Takuto Miyagishima

  7. Department of Hematology, Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital, Sapporo, Japan

    Hiroshi Iwasaki

  8. Department of Hematology, Asahikawa City Hospital, Asahikawa, Japan

    Yasutaka Kakinoki

  9. Department of Hematology, Sapporo City General Hospital, Sapporo, Japan

    Satoshi Yamamoto

  10. Department of Hematology, Tonan Hospital, Sapporo, Japan

    Yoshihito Haseyama

  11. Department of Hematology, Teine Keijinkai Hospital, Sapporo, Japan

    Seisho Ando

  12. Division of Gastroenterology and Hematology/Oncology, Asahikawa Medical University, Asahikawa, Japan

    Motohiro Shindo

  13. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Shuichi Ota

  14. Department of Hematology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan

    Mitsutoshi Kurosawa

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  1. Takeshi Kondo
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  17. Takanori Teshima
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The North Japan Hematology Study Group (NJHSG)

Corresponding author

Correspondence to Takeshi Kondo.

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Conflict of interest

TK has received honoraria from Bristol-Myers Squibb, Novartis, and Ohtsuka Pharmaceutical, a grant from Bristol-Myers Squibb, and research funding from Novartis. SO has received honoraria from Novartis. YO has received honoraria from Novartis and Lonza, a grant from Bristol-Myers Squibb, and research funding from Ohtsuka Pharmaceutical. TT has received honoraria and grants from Bristol-Myers Squibb, Novartis, and Ohtsuka Pharmaceutical. The other authors declare no competing interests.

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Kondo, T., Fujioka, M., Fujisawa, S. et al. Clinical efficacy and safety of first-line nilotinib therapy and evaluation of the clinical utility of the FRET-based drug sensitivity test. Int J Hematol 110, 482–489 (2019). https://doi.org/10.1007/s12185-019-02696-w

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