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Ruxolitinib dose management as a key to long-term treatment success

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Abstract

The Janus kinase 1 (JAK1) and JAK2 inhibitor ruxolitinib is currently the only therapy indicated for intermediate- or high-risk myelofibrosis. Results from clinical trials and experience in clinical practice have shown that ruxolitinib reduces myelofibrosis-related splenomegaly and symptom burden, and improves quality-of-life measures. In addition, ruxolitinib was associated with a survival advantage compared with placebo or conventional therapy in controlled trials. However, owing to the myelosuppressive effects of JAK2 inhibition, ruxolitinib is associated with decreases in hemoglobin and platelet counts, particularly during the first 8–12 weeks of therapy. Close monitoring of blood counts and careful dose management, particularly early in the course of therapy, are essential to avoid unnecessary cytopenias that may prompt premature treatment discontinuation by patients who otherwise would benefit from continued therapy. In general, starting doses and dose reductions should be used as recommended by the prescribing information based on platelet counts. A dose-escalation approach at the start of therapy is only recommended for patients with platelet counts of 50–100 × 109/L. If possible, maximum tolerated doses should be maintained and extended treatment interruptions should be avoided to prevent lack or loss of treatment responses. An individualized dosing approach is key to long-term treatment success.

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Acknowledgments

Medical writing support was provided by Roland Tacke, PhD, of Evidence Scientific Solutions, Philadelphia, PA, USA, and funded by Incyte Corporation.

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, 13400 E. Shea Blvd, Scottsdale, AZ, 85259, USA

    Ruben A. Mesa

  2. Malignant Hematology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

    Rami S. Komrokji

  3. Division of Cancer Medicine, Department of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Srdan Verstovsek

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  1. Ruben A. Mesa
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  2. Rami S. Komrokji
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  3. Srdan Verstovsek
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Correspondence to Ruben A. Mesa.

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Conflict of interest

R. A. M. has received research funding from Genentech, Gilead, Incyte, NS Pharma, and Promedior, and served as a consultant for Novartis. R. S. K. is on Incyte’s advisory board. S. V. has received research funding from AstraZeneca, Bristol-Myers Squibb, Celgene, CTI BioPharma, Geron, Gilead, Incyte, Lilly Oncology, Novartis, NS Pharma, Promedior, and Seattle Genetics and is on Incyte’s advisory board.

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Medical writing support was funded by Incyte Corporation.

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Mesa, R.A., Komrokji, R.S. & Verstovsek, S. Ruxolitinib dose management as a key to long-term treatment success. Int J Hematol 104, 420–429 (2016). https://doi.org/10.1007/s12185-016-2084-1

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  • DOI: https://doi.org/10.1007/s12185-016-2084-1

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