Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial

Abstract

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).

Figures

Figure 1.

Labile plasma iron at baseline, six months and 12 months of deferasirox therapy. Patients with favorable and unfavorable cardiac response at 18 months of therapy are displayed separately. Horizontal line at 0.5 umol/L represents the upper limit of normal for LPI.

Figure 2.

Percentage of patients with increased LPI (LPI > 0.5 uMol, light line) or who were cardiac non-responders at 18 months (dark line) as a function of baseline liver iron concentration (LIC). Plot of labile plasma iron versus LIC. Solid symbols represent patients who did not respond or did not complete 18 months of deferasirox therapy. Open symbols represent patients whose cardiac T2* improved more than 14.7% from baseline after 18 months of deferasirox at 30–40 mg/kg/day. Horizontal line reflects LPI upper limit of normal (0.5 uMol). Vertical lines represent optimal cut offs generated by ROC analysis for detectable LPI (gray line) and cardiac response (black line).

Figure 3.

Receiver Operator Characteristic (ROC) (A) curve for prediction of elevated LPI by liver iron concentration (LIC). Curve represents the trade off between sensitivity and 1-specificity; numbers alongside the curve represent LIC values at critical points. (B) Same representation for the probability of favorable 18 month cardiac response to deferasirox.