A Prospective, Observational Study of the Effectiveness and Safety of a Weekly Fixed Dose of Darbepoetin alfa with Current Practice Iron Management for the Treatment of Chemotherapy-Induced Anemia (CIA): A Subanalysis in Patients (pts) with Lymphoproliferative Malignancies (LPM).

Background: Darbepoetin alfa (Aranesp^®) is a unique erythropoiesis-stimulating protein effective for the treatment of CIA when administered weekly (QW), every 2 weeks (wks) or every 3 wks. Fixed dosing of darbepoetin alfa is routinely used in clinical practice, but little data are available on its patterns of use and the impact of iron status on its effectiveness.

Methods: This was a subanalysis of LPM pts included in a prospective, single-arm, multicenter study conducted in Spain. Pts were ≥ 18 yrs old, anemic (hemoglobin [Hb] ≤11 g/dL), scheduled to receive ≥ 12 wks of chemotherapy, and without iron, vitamin B12, or folate deficiencies. Pts were treated with darbepoetin alfa 150 mcg QW; the dose was to be doubled to 300 mcg QW if Hb increased <1 g/dL after 4 wks. Oral iron (200 mg QD) was recommended if transferrin saturation was ≤ 30%, transferrin was ≥ 400 mcg/dL, and/or ferritin was ≤ 300 mcg/L at any time during the study. The primary endpoint was hematopoietic response (Hb increase ≥ 2 g/dL or Hb ≥ 12g/dL in the absence of transfusions in the previous 28 days). Secondary endpoints included the percentage of pts with functional or absolute iron deficiency and its correlation with response rates, change in FACT-Fatigue score from baseline to end of treatment (EOT), and safety.

Results: Of a total of 293 patients enrolled, 129 had LPM and were included in this analysis. Of the LPM patients, 55% were women, median age was 67.3 yrs (range: 20.6–88.4), median weight was 67 kg (range: 40.5–115.0). Eleven percent had Hodgkin’s disease, 33.9% had non-Hodgkin’s lymphoma. 5.5% had chronic lymphocytic leukemia, and 49.6% had multiple myeloma. Most pts (80.5%) had baseline Hb between 9–11 g/dL; 19.5 % had Hb < 9 g/dL. Darbepoetin alfa was administered for a median of 16 wks (range:1–16). At wk 5, 25.6 % of pts had their dose doubled to 300 mcg QW. The observed hematopoietic response was 70.73% (95%CI: 62.69, 78.77). The proportion of pts transfused from wk 5 to EOT was 12.7%. During the study, 31.5% pts received oral iron, 10.3% developed absolute iron deficiency, and 8% had iron blockade. Mean (95% CI) FACT-Fatigue score increased from 34.1 (32.2, 35.9) to 40.0 (38.2, 41.8) (p<0.0001). Darbepoetin alfa was well tolerated with 2.4% of pts experiencing adverse events considered related to the study drug.

Conclusions: darbepoetin alfa, given as a fixed dose, is an effective and well-tolerated treatment for CIA in pts with LPM. Darbepoetin alfa significantly improved health-related quality of life in this routine clinical practice setting.