Deferasirox (Exjade®, ICL670) Demonstrates Dose-Related Effects on Body Iron Levels Related to Transfusional Iron Intake in Transfusion-Dependent Anemia.

Abstract

Iron overload, a potentially serious consequence of multiple blood transfusions, can be effectively managed with chelation therapy. Deferasirox, an investigational once-daily oral chelator, has been evaluated in a 1 year study of iron-overloaded adult and pediatric patients (n=184) with transfusion-dependent anemia including β-thalassemia, myelodysplastic syndromes (MDS) and Diamond-Blackfan anemia (DBA). Patients were stratified into four daily dose groups (5, 10, 20 and 30 mg/kg) according to baseline liver iron concentration (LIC; 2–3, >3–7, >7–14 and >14 mg Fe/g dw, respectively). Iron balance was determined for all patients, based on transfusional iron intake and chelator-induced iron excretion, derived from the change in LIC during the study (Table 1).Patient characteristics, LIC, serum ferritin and iron excretion/intake ratio during deferasirox treatmentβ-thalassemia (n=85)DBA (n=30)MDS (n=47)Other anemias (n=22)Age*, years24.7 ± 10.016.1 ± 10.365.1 ± 12.535.8 ± 22.9Body weight, kg51.1 ± 14.139.1 ± 18.770.4 ± 12.556.1 ± 18.5Deferasirox dose*, mg/kg23.8 ± 7.223.6 ± 7.420.0 ± 8.321.9 ± 6.5Iron intake*, mg/kg/day0.35 ± 0.120.40 ± 0.110.28 ± 0.140.31 ± 0.19 <0.3, n (%)28 (33)6 (20)25 (53)10 (45) 0.3–0.5, n (%)49 (58)19 (63)20 (43)7 (32) >0.5, n (%)8 (9)5 (17)2 (4)5 (23)Serum ferritin*, ng/mL Baseline4321 ± 28813245 ± 24393343 ± 19783144 ± 1850 Absolute change−386 ± 1626−118 ± 1373−268 ± 2053−750 ± 1517LIC*, mg Fe/g dw(n=76)(n=26)(n=28)(n=17) Baseline19.3 ± 10.918.8 ± 10.715.6 ± 11.915.1 ± 6.2 Absolute change−4.7 ± 8.6−1.6 ± 6.5−5.7 ± 6.3−3.7 ± 6.3Iron excretion/intake ratio1.5 ± 0.901.1 ± 0.461.7 ± 0.931.6 ± 1.48*Mean ± SDTransfusion requirements and iron intake during the study varied widely between diseases. However, LIC and serum ferritin decreases were consistently achieved in all patient groups. More than one-third (38%) of patients, most of whom had MDS or other anemias, had an iron intake rate <0.3 mg/kg/day (average: 0.2 mg/kg/day; corresponding to 5.6 ml RBC/kg/month). In these patients, deferasirox at 10 and 20 mg/kg reduced LIC.Overall, an iron intake- and dose-related response pattern was observed for both LIC and serum ferritin (Figure 1). [Display omitted] According to these results, deferasirox demonstrates the ability to stabilize and effectively decrease body iron levels at doses of 10, 20 and 30 mg/kg/day, depending on the degree of iron intake. In conclusion, dosing of chelation therapy should be guided by a patient's transfusion requirements and the treatment goal, which is either to maintain or reduce body iron.