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Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis

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Abstract

Ruxolitinib, a potent JAK1/JAK2 inhibitor, improved splenomegaly and myelofibrosis-associated symptoms and prolonged survival compared with placebo and best available therapy in the phase 3 COMFORT studies. Although cytopenias were the most common adverse events associated with ruxolitinib treatment, a COMFORT-I analysis showed that they were managed effectively with dose modifications, without a negative impact on the efficacy of ruxolitinib. Subsequently, studies A2202 and AJP01 showed that ruxolitinib is an effective treatment for Japanese patients with myelofibrosis. We conducted a pooled analysis of these two studies (N = 81) to evaluate the association between ruxolitinib dose and changes in spleen volume or symptoms in Japanese patients. Most patients began treatment at 15 or 20 mg twice daily (BID); 70% received a final titrated dose ≥ 10 mg BID. Overall, 91% of patients exhibited spleen volume reductions; patients with final titrated doses ≥ 10 mg BID had larger spleen volume reductions. Similarly, 83% of patients showed improvements in symptom scores; those with a final titrated dose of 20 or 25 mg BID had the greatest reductions. Consistent with COMFORT-I, this pooled analysis indicates that, despite dose adjustments, ruxolitinib provides spleen and symptom control in Japanese patients, with higher doses associated with better responses.

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Acknowledgements

Editorial assistance was provided by Karen Chinchilla, PhD, of ArticulateScience LLC and was funded by Novartis Pharma KK.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University of Yamanashi, 1110 Simokawakita, Chuou-shi, Yamanashi, 409-3898, Japan

    Keita Kirito

  2. Division of Hematology, Department of Medicine, Keio University Hospital, Tokyo, Japan

    Shinichiro Okamoto

  3. Blood Transfusion Service, Mie University Hospital, Mie, Japan

    Kohshi Ohishi

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

    Tetsuzo Tauchi

  5. Department of Medicine, Gunma University Hospital, Gunma, Japan

    Hiroshi Handa

  6. Department of Hematology, Nagoya University Hospital, Nagoya, Japan

    Shigeki Saito

  7. Department of Hematology and Oncology, Japanese Red Cross Nagoya Daini Hospital, Aichi, Japan

    Shigeki Saito

  8. Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan

    Katsuto Takenaka

  9. Department of Gastroenterology and Hematology, University of Miyazaki, Miyazaki, Japan

    Kazuya Shimoda

  10. Department of Hematology and Oncology, Osaka University, Osaka, Japan

    Kenji Oritani

  11. Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan

    Koichi Akashi

  12. Novartis Pharma KK, Tokyo, Japan

    Hikaru Okada, Taro Amagasaki, Kazuyuki Suzuki & Toshio Yonezu

  13. Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan

    Norio Komatsu

Authors
  1. Keita Kirito
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  2. Shinichiro Okamoto
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  3. Kohshi Ohishi
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  4. Tetsuzo Tauchi
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  5. Hiroshi Handa
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  6. Shigeki Saito
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  7. Katsuto Takenaka
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  8. Kazuya Shimoda
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  9. Kenji Oritani
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  10. Koichi Akashi
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  11. Hikaru Okada
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  12. Taro Amagasaki
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  13. Kazuyuki Suzuki
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  14. Toshio Yonezu
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  15. Norio Komatsu
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Corresponding author

Correspondence to Keita Kirito.

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Conflict of interest

KK reports personal fees from Novartis Pharma KK, during conduct of the study. K. Shimoda reports grants and personal fees from Novartis Pharma KK, outside the submitted work. K. Oritani reports personal fees for lectures and scholarship contributions from Novartis Pharma KK, outside the submitted work. HO, TA, K Suzuki, and TY are employees of Novartis Pharma KK. SO, K. Ohishi, TT, HH, SS, KT, KA, and NK have no conflicts of interest to disclose.

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Kirito, K., Okamoto, S., Ohishi, K. et al. Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis. Int J Hematol 107, 92–97 (2018). https://doi.org/10.1007/s12185-017-2332-z

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  • DOI: https://doi.org/10.1007/s12185-017-2332-z

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