Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major.

Abstract

BACKGROUND:

Prospective data on cardiac iron removal are limited beyond one year and longer-term studies are, therefore, important.

DESIGN AND METHODS:

Seventy-one patients in the EPIC cardiac substudy elected to continue into the 3(rd) year, allowing cardiac iron removal to be analyzed over three years.

RESULTS:

Mean deferasirox dose during year 3 was 33.6 ± 9.8 mg/kg per day. Myocardial T2*, assessed by cardiovascular magnetic resonance, significantly increased from 12.0 ms ± 39.1% at baseline to 17.1 ms ± 62.0% at end of study (P<0.001), corresponding to a decrease in cardiac iron concentration (based on ad hoc analysis of T2*) from 2.43 ± 1.2 mg Fe/g dry weight (dw) at baseline to 1.80 ± 1.4 mg Fe/g dw at end of study (P<0.001). After three years, 68.1% of patients with baseline T2* 10 to <20 ms normalized (≥ 20 ms) and 50.0% of patients with baseline T2* >5 to <10 ms improved to 10 to <20 ms. There was no significant variation in left ventricular ejection fraction over the three years. No deaths occurred and the most common investigator-assessed drug-related adverse event in year 3 was increased serum creatinine (n = 9, 12.7%).

CONCLUSIONS:

Three years of deferasirox treatment along with a clinically manageable safety profile significantly reduced cardiac iron overload versus baseline and normalized T2* in 68.1% (32 of 47) of patients with T2* 10 to <20 ms.

• Authors: Dudley J Pennell, John B Porter, Maria Domenica Cappellini, Lee Lee Chan, Amal El-Beshlawy, Yesim Aydinok, Hishamshah Ibrahim, Chi-Kong Li, Vip Viprakasit, Mohsen S Elalfy, Antonis Kattamis, Gillian Smith, Dany Habr, Gabor Domokos, Bernard Roubert, Ali Taher
• Journal: Haematologica (Haematologica) Vol. 97 Issue 6 Pg. 842-8 (Jun 2012) ISSN: 1592-8721 [Electronic] Italy
• PMID: 22271905 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoates
• Iron Chelating Agents
• Triazoles
• Iron
• Deferasirox

Topics

• Adolescent
• Adult
• Benzoates (administration & dosage, therapeutic use)
• Blood Transfusion
• Cardiomyopathies (complications, drug therapy, physiopathology, prevention & control)
• Chelation Therapy
• Child
• Deferasirox
• Drug Administration Schedule
• Heart (drug effects, physiopathology)
• Humans
• Iron (metabolism)
• Iron Chelating Agents (administration & dosage, therapeutic use)
• Iron Overload (complications, drug therapy, physiopathology)
• Longitudinal Studies
• Magnetic Resonance Angiography
• Triazoles (administration & dosage, therapeutic use)
• beta-Thalassemia (complications, drug therapy, physiopathology)