Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias

Abstract

Objectives: It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism.

Methods: The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10-30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias.

Results: Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (-26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (< 0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12).

Conclusions: At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism.

Figure 1

Median serum ferritin levels (±25th/75th percentiles) and mean deferasirox dose (±SD) for all patients over the 1-yr study. *Dotted line indicates a threshold of 2500 ng/mL, serum ferritin levels above which are associated with significant negative outcomes in thalassaemia major (20, 21).

Figure 2

Labile plasma iron (LPI) levels, pre- and postdose administration at baseline and after repeat doses. Individual patient data are shown for patients with (A) production anaemias and (B) haemolytic anaemias. The grey-shaded area indicates a LPI threshold of 0.4 μm (22). Horizontal bars denote mean LPI.

Figure 3

(A) The relationship between baseline predose labile plasma iron (LPI) and transfusion rate in the year prior to study entry. There is a significant correlation (R = 0.58, P = 0.0005, n = 32) between transfusion rate in the year prior to study entry and baseline predose LPI in all patients. Haemolytic anaemias are shown in circles and production anaemias in diamonds. The grey area denotes the healthy reference range. (B) The relationship between baseline predose LPI and baseline serum ferritin. There is a significant relationship (R = 0.47, P = 0.004) between baseline ferritin and baseline predose LPI for all patients. Haemolytic anaemias are shown in circles and production anaemias in diamonds. The grey area denotes the healthy reference range.