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A dose exploration, phase I/II study of administration of continuous erythropoietin receptor activator once every 3 weeks in anemic patients with multiple myeloma receiving chemotherapy

Medical University of Lublin, Lublin, Poland; Medical University, Bialystok, Poland; Medical University of Warsaw, Warsaw, Poland; Gdansk Medical Academy, Gdansk, Poland; Charles University, Prague, Czech Republic; Hoffmann-La Roche, Nutley, NJ, USA.

Correspondence: Anna Dmoszynska, Haematooncology and Bone Marrow Transplantation Department, Medical University of Lublin, ul. Staszica 11, 20081 Lublin, Poland. E-mail: annadmosz{at}o2.pl

Background and Objectives: Continuous erythropoietin receptor activator (C.E.R.A.) is an innovative agent with unique erythropoietin receptor activity and a prolonged half-life, which has the potential for administration at extended dosing intervals. The objectives of this dose-finding study were to evaluate the hemoglobin (Hb) dose-response, pharmacokinetics, and safety of repeated doses of C.E.R.A. given once every 3 weeks to anemic patients with multiple myeloma (MM) receiving chemotherapy.

Design and Methods: This was an exploratory two-stage, open-label, parallel-group, multicenter study. Patients received C.E.R.A. doses of 1.0, 2.0, 3.5, 4.2, 5.0, 6.5, or 8.0 µg/kg once every 3 weeks by subcutaneous injection initially for 6 weeks, followed by a 12-week optional extension period. The primary outcome measures were the average Hb level and its change from baseline over the initial 6-week period, based on values of the slope of the linear regression analysis and the area under the curve. Rates of Hb response (defined as an increase in Hb of 2 g/dL without transfusion) and blood transfusion were also evaluated.

Results: Sixty-four patients entered the study. Dose-related increases in Hb levels were observed during the initial 6-week treatment period for C.E.R.A. doses of 1.0–4.2 µg/kg, with a similar response observed at higher doses. At least 70% of patients receiving 2.0–8.0 µg/kg of C.E.R.A. had Hb responses during the 18-week study. The elimination half-life of C.E.R.A. was found to be long (6.3–9.7 days [151.2–232.8 hours]). All doses were generally well tolerated.

Interpretation and Conclusions: Based on its unique, long elimination half-life, C.E.R.A. has been demonstrated to be an effective and well-tolerated treatment of anemia given once every 3 weeks to patients with multiple myeloma receiving chemotherapy.

Key words: anemia, C.E.R.A., chemotherapy, erythropoietin, multiple myeloma.