Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload

Abstract

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.

Design and 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).

Trial registration: ClinicalTrials.gov NCT00171821.

Figures

Figure 1.

Planned deferasirox doses at core baseline, end of the one-year core and end of the one-year extension study in all patients.

Figure 2.

Changes in myocardial T2* (geometric mean ± 95% CI) over two years in all patients (n=101) and in subgroups with baseline T2* >5 to 5 to

Figure 3.

Changes in LVEF (mean ± SD) over two years in all patients (n=101) and in subgroups with baseline T2* >5 to 5 to

Figure 4.

Changes in LIC (mean ± SD) over two years in all patients (n=101) and in subgroups with baseline T2* >5 to 5 to

Figure 5.

Changes in serum ferritin (median ± 25th/75th percentiles) over two years in all patients (n=101) and in subgroups with baseline T2* >5 to <10 ms (n=39), and T2* 10 to <20 ms (n=62). The 24-month value includes all patients who received study medication and had a serum ferritin measurement at baseline and post-month 12, analyzed using LOCF analysis (n=101).