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International Journal of Hematology

, Volume 107, Issue 1, pp 92–97 | Cite as

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

  • Keita Kirito
  • Shinichiro Okamoto
  • Kohshi Ohishi
  • Tetsuzo Tauchi
  • Hiroshi Handa
  • Shigeki Saito
  • Katsuto Takenaka
  • Kazuya Shimoda
  • Kenji Oritani
  • Koichi Akashi
  • Hikaru Okada
  • Taro Amagasaki
  • Kazuyuki Suzuki
  • Toshio Yonezu
  • Norio Komatsu
Original Article

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.

Keywords

Myelofibrosis JAK inhibitor Ruxolitinib Japanese patients 

Notes

Acknowledgements

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

Compliance with ethical standards

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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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Keita Kirito
    • 1
  • Shinichiro Okamoto
    • 2
  • Kohshi Ohishi
    • 3
  • Tetsuzo Tauchi
    • 4
  • Hiroshi Handa
    • 5
  • Shigeki Saito
    • 6
    • 7
  • Katsuto Takenaka
    • 8
  • Kazuya Shimoda
    • 9
  • Kenji Oritani
    • 10
  • Koichi Akashi
    • 11
  • Hikaru Okada
    • 12
  • Taro Amagasaki
    • 12
  • Kazuyuki Suzuki
    • 12
  • Toshio Yonezu
    • 12
  • Norio Komatsu
    • 13
  1. 1.Department of Hematology and OncologyUniversity of YamanashiChuou-shiJapan
  2. 2.Division of Hematology, Department of MedicineKeio University HospitalTokyoJapan
  3. 3.Blood Transfusion ServiceMie University HospitalMieJapan
  4. 4.Department of HematologyTokyo Medical UniversityTokyoJapan
  5. 5.Department of MedicineGunma University HospitalGunmaJapan
  6. 6.Department of HematologyNagoya University HospitalNagoyaJapan
  7. 7.Department of Hematology and OncologyJapanese Red Cross Nagoya Daini HospitalAichiJapan
  8. 8.Center for Cellular and Molecular MedicineKyushu University HospitalFukuokaJapan
  9. 9.Department of Gastroenterology and HematologyUniversity of MiyazakiMiyazakiJapan
  10. 10.Department of Hematology and OncologyOsaka UniversityOsakaJapan
  11. 11.Department of Medicine and Biosystemic ScienceKyushu UniversityFukuokaJapan
  12. 12.Novartis Pharma KKTokyoJapan
  13. 13.Department of HematologyJuntendo University School of MedicineTokyoJapan

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