High-dose epoetin alfa as induction treatment for severe anemia in multiple myeloma patients

Abstract

Anemia is a common finding in patients with multiple myeloma (MM): it is present in two-thirds of patients (pts) at diagnosis and reflects the course of the disease, since it worsens during resistant or progressive disease and ameliorates when the disease is controlled by treatment [1, 2]. Generally, anemia during myeloma is normochromic and normocytic, characterized by shortened erythrocyte survival with failure of bone marrow to compensate red cell production. The multifactor basis of bone marrow impairment includes: (a) impaired availability of storage iron, (b) inadequate erythropoietin response to the level of anemia, and (c) overproduction of cytokines capable of direct erythropoiesis inhibition. These cytokines (including tumor necrosis factor, interleukin-1 and interleukin-6) may also decrease reutilization of iron stores from reticuloendothelial cells and may interfere with kidney erythropoietin production [3]. Recombinant human erythropoietin (rHuEPO) has been extensively used throughout the course of the disease to increase hemoglobin (Hb) concentration, reduce transfusion requirement and improve the quality of life. Treatment of anemia in lymphoproliferative disorders with erythropoiesis-stimulating agents (ESA) has been shown to be safe, efficacious and effective. Response rate (RR) varied from 31 to 78%, according to the criteria utilized for response [4]. In MM, RR was influenced by the disease duration, ratio between observed and predicted serum erythropoietin concentration and Epo dose. RR at 4 weeks (wk) represents the most powerful predictor of a durable response [5]. Recently, ASCO/ASH guidelines for the use of epoetin and darbepoetin have been revised: FDA-approved starting dose of epoetin is 150 IU/kg 3 times/week or 40,000 IU/week subcutaneously; FDAapproved starting dose of darbepoetin is 2.25 lg/kg/week or 500 lg every 3 week subcutaneously. Alternative starting doses or dosing schedules have shown no consistent differences in transfusion and Hb response, although they may be considered to improve cost/effectiveness. Dose escalation should follow those approved by FDA; no convincing evidences indicate that other schedules may be associated with better results. The threshold for initiating ESA therapy should be a concentration of Hb B 10 g/dL [6]. The aim of this study is to evaluate the safety and efficacy of a regimen based on rHuEPO alfa 40000 IU twice/week as starting dose with weekly IV iron supplementation in MM pts with severe anemia. Between January 2003 and March 2004, 20 pts (10 M/ 10 F) with MM were enrolled in this open-label trial. The starting dose consisted of 40000 IU subcutaneously twice/ week for 5 doses (up to 8 doses if no major response was obtained at week 3), maintained by rHuEPO at the conventional schedule in the responder patients. All pts received iron supplementation (oral or IV). The main pretreatment characteristics were the following: median age 67.5 years (58–81); 9 pts were in first line treatment, 6 pts in second line and 5 received more than 3 lines of T. Caravita A. Siniscalchi P. Niscola S. Amadori P. de Fabritiis Department of Hematology, University ‘‘Tor Vergata’’, St. Eugenio Hospital, Rome, Italy