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A randomized controlled trial comparing darbepoetin alfa doses in red blood cell transfusion-dependent patients with low- or intermediate-1 risk myelodysplastic syndromes

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Abstract

Darbepoetin alfa (DA) is a standard treatment for anemia in lower-risk MDS. However, to date there has been no comparative study to investigate the initial dosage. We, thus, conducted a randomized controlled trial to elucidate the optimal initial dosage of DA. International Prognostic Scoring System low or intermediate-1 risk MDS patients with hemoglobin levels ≤9.0 g/dL, serum erythropoietin levels ≤500 mIU/mL, and red blood cell transfusion dependency were enrolled. Patients were randomized to receive DA either at 60, 120, or 240 μg/week for 16 weeks followed by continuous administration with dose adjustment up to 48 weeks. Of 17, 18, and 15 patients in the 60, 120, and 240 μg DA groups included in the efficacy analysis, 64.7, 44.4, and 66.7 %, respectively, achieved the primary endpoint (major or minor erythroid response), while 17.6, 16.7, and 33.3 % achieved major erythroid responses in the initial 16-week period. No clinically significant safety concerns were identified. DA reduced the transfusion requirements effectively and safely in transfusion-dependent, lower-risk MDS patients. Given the highest achievement rate of the major erythroid response in the 240 μg group and the absence of dose-dependent adverse events, 240 μg weekly is the optimal initial dosage.

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Acknowledgments

We would like to thank all of the participating patients and their families as well as investigators, research nurses, study coordinators, and operations staff.

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Correspondence to Kinuko Mitani.

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Conflict of interest and sources of funding

Kyowa Hakko Kirin Co., Ltd. sponsored this clinical study and was responsible for medical monitoring and auditing. R. Shimazaki is an employee of and owns stock in Kyowa Hakko Kirin Co., Ltd. J. H. Jang, H. Harada, H. Shibayama, H. J. Kim, and K. Mitani were principle investigators for this trial. HJ Kim and K Mitani were coordinating investigators of this trial and received consulting fees from Kyowa Hakko Kirin Co., Ltd. K. Sawada was the medical adviser of this trial and received consulting fees from Kyowa Hakko Kirin Co., Ltd. H. Harada has received grant from Nippon-Shinyaku Co., Ltd., Novartis Pharma outside the submitted work, and personal fees from Nippon-Shinyaku Co., Ltd., Novartis Pharma, and Celgene K. K. outside the submitted work. H. Shibayama has received personal fee from Kyowa Hakko Kirin Co., Ltd. outside the submitted work. K. Mitani has received grant from Kyowa Hakko Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Novartis Pharma, Bristol-Myers Squibb outside the submitted work.

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Jang, J.H., Harada, H., Shibayama, H. et al. A randomized controlled trial comparing darbepoetin alfa doses in red blood cell transfusion-dependent patients with low- or intermediate-1 risk myelodysplastic syndromes. Int J Hematol 102, 401–412 (2015). https://doi.org/10.1007/s12185-015-1862-5

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  • DOI: https://doi.org/10.1007/s12185-015-1862-5

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