Optimizing Iron Chelator Treatment in Cardiac and Hepatic Siderosis: Efficacy of Divided Deferasirox (EXJADER) – Doses
Authors: Grosse Regine , Jarisch Andrea , Yamamura Jin , Nielsen Peter , Fischer Roland , Janka Gritta 
Published: October 2019

Abstract
Abstract 2110

Introduction:
Iron chelation is the life-saving therapy in patients with chronic transfusion therapy. Treatment with deferoxamine, deferiprone or deferasirox has dramatically improved the life expectancy, but still myocardial siderosis and hepatic siderosis is cause of morbidity and mortality in regularly transfused patients with ß-thalassemia major (TM) or Diamond-Blackfan Anemia (DBA).
Deferasirox (DSX) a once-daily oral iron chelator has demonstrated efficacy in reducing hepatic iron and body iron burden, as well as cardiac iron. But in patients with severe cardiac siderosis (T2* ≤ 10ms) a combination therapy with deferiprone (Ferriprox®) and deferoxamine (Desferal®) is the recommended therapy. However, some patients will not benefit from this treatment due to unacceptable toxicity, poor response or noncompliance.

Method:
We tested a twice-daily deferasirox (Exjade®) -dose with special respect to its efficacy on reducing cardiac iron overload. A group of six patients with severe secondary siderosis was studied, TM (n=5) and DBA (n=1), (5 females, age 8–37 years, mean age 27.7 years). In all patients the liver iron concentration was measured repeatedly by SQUID biosusceptometry or by magnetic resonance imaging (MRI) using the MRI-R2 technique (St. Pierre et al, 2005). In 4 patients with severe cardiac siderosis (T2* ≤ 10ms) we also followed the cardiac iron concentration by MRI using a single breath-hold, multi-echo T2* method. Patients received a daily DSX dose of 19 mg/kg/d – 45 mg/kg/d, with a mean dose of 32 mg/kg/d.

Results:
The mean initial liver iron concentration of 2.7 mg/g-liver (0.96 – 5.5mg/g) decreased to 1.5 mg/g-liver (0.6 – 3.9 mg/g). The mean monthly liver iron clearance was 6.8%/month (1.7 – 16.8%/month) in a treatment interval of 4 – 26 months (mean: 9.8 months), the patients demonstrated a significant liver iron reduction of 44.4%.
The mean serum ferritin was reduced from 3048 μg/l to 1786 μg/l.
The mean monthly cardiac iron clearance was 3.1%/month (1.2 – 4.7%/month) and the mean T2* value improved from 9.5 ms to 14.3 ms (+50%). We showed a substantial improvement in patients with severe cardiac siderosis with a T2* improvement of 50 % after a mean treatment period of 12 months with a mean DSX dose of 32 mg/kg/d. In comparison, an improvement of 23.8% was found in 6 patients with T2* < 10 ms, after a treatment period of 18 months with a once daily DSX mean dose of 38 mg/kg/d (Pathare et al, 2010). Other authors reported an improvement of 10.8% in 47 patients (T2* < 10 ms, treatment period 12 months) with a once daily DSX mean dose of 32 mg/kg/d (Pennell et al, 2009).
No severe side effects were seen in our patients and only minor increases in creatinine values, which were reversible with dose reduction.

Conclusion:
Deferasirox divided in twice daily doses is a safe and effective therapy for patients with severe cardiac iron overload (T2* < 10ms) or hepatic iron overload, who do not well tolerate a combination therapy with deferiprone and deferoxamine.

Disclosures:
Off Label Use: Deferasirox (Exade)is given instead of a once daily dose, in a twice daily divided dose. The daily dose of Deferasirox is in recommended range.