Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study

Abstract

Objectives/methods: This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or beta-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC).

Results: In patients with baseline LIC > or = 7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 +/- 0.14 mg/kg/d; greatest in DBA: 0.4 +/- 0.11 mg/kg/d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.

Conclusions: Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups.

Figure 1

Separate regression lines derived from a linear model for each disease are shown in this figure together with symbols indicating the mean changes in LIC and ferritin by disease group and dose (as summarised in Table 2). When analysing the data across disease groups (regression line not shown), an overall LIC change over 1 yr is predicted as −3.36 + 0.003 times change in ferritin (Pearson’s correlation coefficient = 0.59). Based on this linear model, a reduction in ferritin of 1000 μg/L predicts a reduction of approximately 6 mg Fe/g dw in LIC.

Figure 2

Iron excretion across dose and disease groups. The average iron excretion in mg/kg/d (±SD) is shown by disease group for doses above 5 mg/kg/d. There is a dose effect on iron excretion (P < 0.001), with no statistically significant difference in disease groups (P = 0.14). The overall average iron excretion is 0.22, 0.44 and 0.53 mg/kg/d for doses of 10, 20 and 30 mg/kg/d, respectively.