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Treatment-free remission after first-line dasatinib treatment in patients with chronic myeloid leukemia in the chronic phase: the D-NewS Study of the Kanto CML Study Group

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Abstract

Treatment outcomes for chronic myeloid leukemia (CML) have dramatically improved with the development of tyrosine kinase inhibitors (TKI). However, due to the improved prognosis for CML, problems have arisen from long-term administration of TKI. The present study sought to verify whether more patients could achieve treatment-free remission (TFR) after stopping the administration of dasatinib using dasatinib as frontline treatment. Treatment-naïve chronic phase CML cases were treated with dasatinib as frontline treatment. Dasatinib treatment was stopped for 26 patients who achieved deep molecular response (DMR) within 24 months and were able to maintain DMR for an additional 2 years. Ten patients (38.5%) achieved DMR maintenance after 12 months. Recurrence was confirmed in 16 patients, and the median recurrence-free survival time was 5.1 months. The cumulative DMR rates at six and 12 months after restarting treatment were 84.6% and 100%, respectively. The results of this study demonstrated that the DMR maintenance rate after 12 months was 38.5%, which was not significantly different from previous TKI stop trials. The 2-year dasatinib administration period after reaching DMR did not contribute to improve TFR rates. These results suggest that the type of TKI is not associated with better TFR rates.

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Acknowledgements

This study was supported by the Epidemiological and Clinical Research Information Network (ECRIN). This research was conducted as Investigator Sponsored Research with financial support by Bristol-Myers Squibb Co., Ltd.

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Author notes

  1. Hiroki Yamaguchi and Koiti Inokuchi contributed equally to this study.

Authors and Affiliations

  1. Department of Hematology Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan

    Hiroki Yamaguchi & Koiti Inokuchi

  2. Department of Hematology, National Hospital Organization Disaster Medical Center, Tachikawa, Japan

    Naoki Takezako

  3. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Kazuteru Ohashi & Hisashi Sakamaki

  4. Interfactulty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan

    Koji Oba

  5. Department of Hematology, Ome Municipal General Hospital, Tokyo, Japan

    Takashi Kumagai

  6. Department of Hematology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan

    Yasuji Kozai

  7. Division of Hematology and Oncology, Japanese Red Cross Society, Narita Red Cross Hospital, Narita, Japan

    Hisashi Wakita

  8. Department of Hematology, Yokohama City Minato Red Cross Hospital, Yokohama, Japan

    Koh Yamamoto

  9. Hematology Division, Showa General Hospital, Tokyo, Japan

    Akira Fujita

  10. Division of Hematology and Oncology, Gunma Prefectural Cancer Center, Ohta, Japan

    Tadahiko Igarashi

  11. Department of Hematology, National Hospital Organization, Mito Medical Center, Higashiibarakigun, Ibaraki, Japan

    Chikashi Yoshida

  12. Department of Hematology, Tokyo Medical University, Tokyo, Japan

    Kazuma Ohyashiki

  13. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Shinichiro Okamoto

  14. Tokai Central Hospital, Kakamigahara, Japan

    Junichi Sakamoto

  15. Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Koji Oba

Authors
  1. Hiroki Yamaguchi
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  2. Naoki Takezako
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  5. Takashi Kumagai
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  6. Yasuji Kozai
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  8. Koh Yamamoto
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  9. Akira Fujita
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  10. Tadahiko Igarashi
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Corresponding author

Correspondence to Hiroki Yamaguchi.

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Conflict of interest

Hiroki Yamaguchi received honoraria from Novartis Co., Ltd., Kazuteru Ohashi received research support from Celgene Co., Ltd., Jansen Pharma Co., Ltd., Chugai Pharma Co., Ltd., Bristol-Myers Squibb Co., Ltd., Novartis Pharma Co., Ltd., and Kirin Co., Ltd., and served as consultant and advisor of Celgene Co., Ltd., Novartis Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Ariad Co., Ltd., and honoraria from Novartis Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Nippon Shinyaku Co., Ltd. Koji Oba received honoraria from Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo Pharmaceutical Co., Ltd., Asahi Kasei Pharma Corp., Takeda Pharmaceuticals, Co., Ltd., and Ono Pharmaceutical Co., Ltd. Chikashi Yoshida received honoraria from Bristol-Myers Squibb Co., Ltd., Novartis Co., Ltd., Pfizer Co., Ltd., and Otsuka Pharmacology Co., Ltd.. Takashi Kumagai received honoraria from Bristol-Myers Squibb Co., Ltd., Novartis Co., Ltd., Pfizer Co., Ltd., and Otsuka Pharmacology Co., Ltd.. Shinichiro Okamoto received research support and honoraria from Novartis Co., Ltd., Bristol-Myers Squibb Co., Ltd., Pfizer Co., Ltd., and Otsuka Co., Ltd., Koiti Inokuchi received research support from Celgene Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Ono Pharmaceutical Co., Ltd., and received honoraria from Novartis Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Pfizer Co., Ltd.

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Yamaguchi, H., Takezako, N., Ohashi, K. et al. Treatment-free remission after first-line dasatinib treatment in patients with chronic myeloid leukemia in the chronic phase: the D-NewS Study of the Kanto CML Study Group. Int J Hematol 111, 401–408 (2020). https://doi.org/10.1007/s12185-019-02801-z

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