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.

Figure 1.

(A) Geometric mean cardiac T2* ± 95% CI during deferasirox treatment for three years; and (B) shift in proportion of patients with severe, mild-to-moderate and normalized cardiac T2* values at baseline and EOS.

Figure 2.

Mean cardiac iron concentration ± SD during 3-year deferasirox treatment.

Figure 3.

Mean LVEF ± SD during 3-year deferasirox treatment.

Figure 4.

(A) Mean LIC ± SD; and (B) median serum ferritin ± interquartile range during deferasirox treatment for up to three years.

Figure 5.

(A) Frequency of the most common (≥5%) investigator-assessed drug-related AEs; (B) mean creatinine clearance ± SD over time during deferasirox treatment for up to three years (Cockcroft–Gault formula); (C) mean creatinine clearance ± SD over time during deferasirox treatment for up to three years (MDRD formula).