A randomized controlled trial comparing darbepoetin alfa doses in red blood cell transfusion-dependent patients with low- or intermediate-1 risk myelodysplastic syndromes.
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.
Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. smcjunhojang@gmail.com.
Jun Ho
JH
Jang
Department of Hematology and Oncology, Hiroshima University Hospital, Hiroshima, Japan.|Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.
Hironori
H
Harada
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Hirohiko
H
Shibayama
R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
Ryutaro
R
Shimazaki
Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Korea.
Hyeoung-Joon
HJ
Kim
Akita University, Akita, Japan.
Kenichi
K
Sawada
Department of Hematology and Oncology, Dokkyo Medical University School of Medicine, 880, Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi, 321-0293, Japan. kinukom-tky@umin.ac.jp.
Kinuko
K
Mitani
D000368:Aged; D000369:Aged, 80 and over; D000068256:Darbepoetin alfa / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D017707:Erythrocyte Transfusion; D006801:Humans; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000628:therapy*; D012307:Risk Factors
D000068256:Darbepoetin alfa
Darbepoetin alfa; EPO; Erythropoiesis-stimulating agent; MDS; Myelodysplastic syndromes