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We present results from a prospective, multicenter, open-label, single-arm study evaluating response of cardiac and liver iron to deferasirox therapy for 18 months. Twenty-eight patients with abnormal T2* and normal left ventricular ejection fraction were enrolled from 4 US centers. All patients initially received deferasirox doses of 30 to 40 mg/kg per day. Patients were severely iron overloaded: mean liver iron concentration (LIC) 20.3 mg Fe/g dry weight, serum ferritin 4417 ng/mL, and cardiac T2* 8.6 ms. In the intent-to-treat population, 48% reached the primary endpoint (cardiac T2* improvement at 18 months, P = not significant). There were 2 deaths: 1 from congestive heart failure and 1 from sepsis. In the 22 patients completing the trial, LIC and cardiac T2* improvements were 16% (P = .06) and 14% (P = .07), respectively. Cardiac T2* improvement (13 patients) was predicted by initial LIC, final LIC, and percentage LIC change, but not initial cardiac T2*. Cardiac iron improved 24% in patients having LIC in the lower 2 quartiles and worsened 8.7% in patients having LIC in the upper 2 quartiles. Left ventricular ejection fraction was unchanged at all time points. Monotherapy with deferasirox was effective in patients with mild to moderate iron stores but failed to remove cardiac iron in patients with severe hepatic iron burdens. This study was registered at www.clinicaltrials.gov as #NCT00447694.

The US04 trial was a multicenter, open-label, single arm trial of deferasirox monotherapy (30–40 mg/kg/day) for 18 months. Cardiac iron response was bimodal with improvements observed in patients with mild to moderate initial somatic iron stores; relationship of cardiac response to labile plasma iron is now presented. Labile plasma iron was measured at baseline, six months, and 12 months. In patients having a favorable cardiac response at 18 months, initial labile plasma iron was elevated in only 31% of patients at baseline and no patient at six or 12 months. Cardiac non-responders had elevated labile plasma iron in 50% of patients at baseline, 50% patients at six months, and 38% of patients at 12 months. Risk of abnormal labile plasma iron and cardiac response increased with initial liver iron concentration. Persistently increased labile plasma iron predicts cardiac non-response to deferasirox but labile plasma iron suppression does not guarantee favorable cardiac outcome. Study registered at www.clinicaltrials.gov (NCT00447694).

The trial CICL670AUS04 was a single-arm, open-label study of the cardiac efficacy of 18 months of deferasirox monotherapy [1]. Cardiac response in this study was related to the degree of liver siderosis. Patients with mild to moderate liver siderosis improved their cardiac T2* while more severely siderotic patients did not, regardless of initial cardiac iron burden. In this letter, we report 2-year data in those patients who completed a 6-month extension phase (N 5 10). Cardiac and liver iron improved steadily during the 24-month period, with final cardiac T2* and LIC improving 37% and 27%, respectively, in this cohort. Serum ferritin and LVEF were not statistically different at anytime-point. When the extension phase (18-24 months) was considered in isolation, serum ferritin, liver iron concentration, and left ventricular ejection fraction were nearly identical to 18 month results. Despite this, cardiac T2* continued to trend higher, increasing 12.7% from 9.5 ms to 10.7 ms (P 5 0.06). Thus defersirox continued to demonstrate cardiac efficacy in patients with mild to moderate hepatic siderosis throughout 2 years of therapy.