Prospective Comparison on Cardiac and Hepatic Iron and Cardiac Function by MR in Thalassemia Major Patients Treated with Combination Deferiprone–Desferrioxamine Versus Deferiprone and Desferrioxamine in Monoterapy,

Using T2* Magnetic Resonance (MR) a randomized placebo controlled study from Sardinia demonstrated combination therapy with deferiprone and desferrioxamine (DFP+DFO) significantly more effective than DFO in improving myocardial iron. One non-randomized study from Sardinia and one observational study from Greece seem to confirm for DFP+DFO therapy the most rapid clearance of cardiac iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with DFP+DFO versus DFP and DFO in monotherapy. The aim of our multi-centre study was to assess prospectively in a large clinical setting the efficacy of the DFP+DFO versus DFP and DFO in TM patients by quantitative MR.

Among the 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans We evaluated prospectively the 51 patients treated with DFP+DFO versus the 39 patients treated with DFP and the 74 patients treated. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images.

The dosages were: combined therapy DFP 61.9±24.3 mg/kg per 6.1±1.4 days/week and DFO 40.7±6.0 per 3.5±1.1 days/week; DFP 73±13 mg/kg per 6.1±1.4 days/week; DFO 40.7±6.5 per 5.4±0.93 days/week. Excellent/good levels of compliance were comparable in the DFP+DFO (90.2%) versus DFP (94.9%) and DFO (95.9%) groups. The percentage of patients who maintained a normal global heart T2* value (≥20 ms) was comparable between DFP+DFO (96%) versus (100%) and DFO (98.1%) groups. Among the patients with myocardial iron overload at baseline (global heart T2*<20 ms), in all three groups there was a significant improvement in the global heart T2* values (combination: P=0.001; deferiprone: P=0.015 and desferrioxamine: P=0.007) and a significant reduction in the number of segments with an abnormal T2* value (combination: P=0.004; deferiprone: P=0.012 and desferrioxamine: P=0.002). Only in the deferiprone group there was a significant improvement in the left ventricular (LV) ejection fraction (EF) (P=0.045) while improvement in the right ventricular (RV) EF was significant in both combination (P=0.024) and deferiprone (P=0.001) groups. The changes in the global heart T2* as well as in biventricular function were not significantly different in DFO+DFP versus DFO or DFP groups (Table 1). After correction for influential covariates statistically different at baseline (global heart, age and HIC), the changes in global heart T2* values between the combination and the desferrioxamine groups became statistically different (P=0.014). Among the patients with hepatic iron at baseline (T2*<9.2 ms), the improvement in the liver T2* values was significant in the combination and in the desferrioxamine groups (combination: 4.9±6.0 ms P<0.0001; deferiprone: 2.1±4.8 ms P=0.070 and desferrioxamine: 2.0±3.5 ms P=0.010). The increase in liver T2* values was higher in combination versus deferiprone group, with a P-value near to the statistically significance (P=0.062); after covariates adjustment for the variable statistically different at baseline (serum ferritin) the significance was reached (P=0.043). The increase in liver T2* values was significant higher in combination than in desferrioxamine group (P=0.008), even after covariates adjustment.

Prospectively in TM patients at the dosages used in the clinical practice combined DFP+DFO showed superior reduction in myocardial iron only versus the DFO in monotherapy and it did not show better improvement in biventricular function in comparison to DFO and DFP monotherapy. On the other hand, combined DFP+DFO was significantly more effective in the reduction of the liver iron versus DFO and DFP in monotherapy.

Pepe:Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy.