Deferasirox (Exjade®, ICL670) Demonstrates Dose-Related Effects on Body Iron Levels Related to Transfusional Iron Intake in Transfusion-Dependent Anemia.
Authors: Greenberg P. , Dine G. , Ganser A. , Verhoef G. , DeBusscher L. , Quarta G. , Zachée P. , Alimena G. , Jeng M. , Tchernia G. , Gathmann I. , Alberti D. , Rabault B. 
Published: April 2020

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, &gt;3–7, &gt;7–14 and &gt;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 treatment β-thalassemia (n=85) DBA (n=30) MDS (n=47) Other anemias (n=22) *Mean ± SD Age*, years 24.7 ± 10.0 16.1 ± 10.3 65.1 ± 12.5 35.8 ± 22.9 Body weight, kg 51.1 ± 14.1 39.1 ± 18.7 70.4 ± 12.5 56.1 ± 18.5 Deferasirox dose*, mg/kg 23.8 ± 7.2 23.6 ± 7.4 20.0 ± 8.3 21.9 ± 6.5 Iron intake*, mg/kg/day 0.35 ± 0.12 0.40 ± 0.11 0.28 ± 0.14 0.31 ± 0.19     &lt;0.3, n (%) 28 (33) 6 (20) 25 (53) 10 (45)     0.3–0.5, n (%) 49 (58) 19 (63) 20 (43) 7 (32)     &gt;0.5, n (%) 8 (9) 5 (17) 2 (4) 5 (23) Serum ferritin*, ng/mL     Baseline 4321 ± 2881 3245 ± 2439 3343 ± 1978 3144 ± 1850     Absolute change −386 ± 1626 −118 ± 1373 −268 ± 2053 −750 ± 1517 LIC*, mg Fe/g dw (n=76) (n=26) (n=28) (n=17)     Baseline 19.3 ± 10.9 18.8 ± 10.7 15.6 ± 11.9 15.1 ± 6.2     Absolute change −4.7 ± 8.6 −1.6 ± 6.5 −5.7 ± 6.3 −3.7 ± 6.3 Iron excretion/intake ratio 1.5 ± 0.90 1.1 ± 0.46 1.7 ± 0.93 1.6 ± 1.48
Transfusion 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 &lt;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).
Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year
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.