Darbepoetin‐alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation: A prospective multicenter randomized trial

Abstract

We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 μg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n = 24), 79% in Arm 2 (n = 25), and 100% in Arm 3 (n = 23; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n = 46) than in Arm 2 (n = 50; P = 0.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P < 0.0001), i.v. iron administration (P = 0.0010), high baseline Hb (P < 0.0001), and low baseline creatinine (P = 0.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post‐transplant. I.v. iron sucrose further improves erythroid recovery. Am. J. Hematol. 88:990–996, 2013. © 2013 Wiley Periodicals, Inc.

Serum hepcidin following autologous hematopoietic cell transplantation: an illustration of the interplay of iron status, erythropoiesis and inflammation

“…Therefore, we decided to investigate the long-term kinetics of hepcidin after HCT in a group of patients participating in a clinical trial of post-transplant DA with and without intravenous iron therapy. 8 In our study, hepcidin levels prior to HCT were not increased compared to healthy controls.…”

European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications

“…ESAs mainly reduce transfusion requirements and improve quality of life. [36][37][38][39][40] Predictors of response to ESAs include the ratio of observed to expected Hb (<0.9) and the preserved BM function, reflected by the platelet counts (>150x10 9 /L). 33,38,41 A systematic review of the use of ESAs in more than 20,000 cancer patients confirmed that their use reduced the relative risk of transfusions due to increase of erythroid responses, but there was evidence that ESAs increased mortality during ESA administration and thus decreased OS.…”

Iron sucrose – characteristics, efficacy and regulatory aspects of an established treatment of iron deficiency and iron-deficiency anemia in a broad range of therapeutic areas

“…In multiple myeloma or lymphoma patients after autologous hematopoietic cell transplantation, supplementation of darbepoetin-a with IS (200 mg iron on days 28, 42 and 56 post-transplant) increased the percentage of patients with Hb increase ‡ 2 g/dl from 88 to 100% and reduced the median time to response from 28 to 25 days (p = 0.0231) compared to no iron supplementation [63]. The percentage of patients requiring RBC transfusions and the cumulative darbepoetin-alfa dose were significantly lower in the IS arm (0 vs 11.1%; p = 0.0276 and 1210 vs 1440 µg; p = 0.015, respectively).…”