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

• Published in: Haematologica (Roma) Vol. 97; no. 6; pp. 842 - 848
• Main Authors: PENNELL, Dudley J, PORTER, John B, KATTAMIS, Antonis, SMITH, Gillian, HABR, Dany, DOMOKOS, Gabor, ROUBERT, Bernard, TAHER, Ali, DOMENICA CAPPELLINI, Maria, LEE LEE CHAN, EL-BESHLAWY, Amal, AYDINOK, Yesim, IBRAHIM, Hishamshah, LI, Chi-Kong, VIPRAKASIT, Vip, ELALFY, Mohsen S
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01-06-2012
• Subjects: Adolescent; Adult; Anemias. Hemoglobinopathies; Benzoates - administration & dosage; Benzoates - therapeutic use; beta-Thalassemia - complications; beta-Thalassemia - drug therapy; beta-Thalassemia - physiopathology; Biological and medical sciences; Blood Transfusion; Cardiomyopathies - complications; Cardiomyopathies - drug therapy; Cardiomyopathies - physiopathology; Cardiomyopathies - prevention & control; Chelation Therapy; Child; Diseases of red blood cells; Drug Administration Schedule; Heart - drug effects; Heart - physiopathology; Hematologic and hematopoietic diseases; Humans; Iron - metabolism; Iron Chelating Agents - administration & dosage; Iron Chelating Agents - therapeutic use; Iron Overload - complications; Iron Overload - drug therapy; Iron Overload - physiopathology; Longitudinal Studies; Magnetic Resonance Angiography; Medical sciences; Original and Brief Reports; Triazoles - administration & dosage; Triazoles - therapeutic use; Human; Hemoglobinopathy; Hematology; Hemopathy; Iron; Genetic disease; Heavy metal; Deferasirox; Hemolytic anemia; β-Thalassemia; myocardial T2; Chelating agent; Myocardium; Lead; iron chelation; Circulatory system; β-thalassemia major
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2011.049957

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