Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload.
BACKGROUND
The efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with β-thalassemia major in the cardiac sub-study of the EPIC trial.


METHODS
Eligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years.


RESULTS
Baseline myocardial T2* was severe (> 5 to < 10 ms) in 39 patients, and moderate-to-mild (10 to < 20 ms) in 62 patients. Mean deferasirox dose was 33.1 ± 3.7 mg/kg/d in the one-year core study increasing to 36.1 ± 7.7 mg/kg/d during the second year of treatment. Geometric mean myocardial T2* increased from a baseline of 11.2 to 14.8 ms at two years (P < 0.001). In patients with moderate-to-mild baseline T2*, an increase was seen from 14.7 to 20.1 ms, with normalization (≥ 20 ms) in 56.7% of patients. In those with severe cardiac iron overload at baseline, 42.9% improved to the moderate-to-mild group. The incidence of drug-related adverse events did not increase during the extension relative to the core study and included (≥ 5%) increased serum creatinine, rash and increased alanine aminotransferase.


CONCLUSIONS
Continuous treatment with deferasirox for two years with a target dose of 40 mg/kg/d continued to remove iron from the heart in patients with β-thalassemia major and mild, moderate and severe cardiac siderosis. (Clinicaltrials.gov identifier: NCT 00171821).
Royal Brompton Hospital, London, UK. d.pennell@ic.ac.uk
Dudley J
DJ
Pennell
John B
JB
Porter
Maria Domenica
MD
Cappellini
Lee Lee
LL
Chan
Amal
A
El-Beshlawy
Yesim
Y
Aydinok
Hishamshah
H
Ibrahim
Chi-Kong
CK
Li
Vip
V
Viprakasit
Mohsen Saleh
MS
Elalfy
Antonis
A
Kattamis
Gillian
G
Smith
Dany
D
Habr
Gabor
G
Domokos
Bernard
B
Roubert
Ali
A
Taher
D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000627:therapeutic use*; D002648:Child; D000077588:Deferasirox; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000139:chemically induced / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D014230:Triazoles / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy*
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox