Deferiprone Versus Sequential Deferiprone-Deferoxamine Treatment in Thalassemia Major: A Five Years Multicenter Randomized Clinical Trial under the Auspices of the Society for the Study of Thalassemia and Hemoglobinopathies (SoSTE).
Authors: Maggio Aurelio , Capra Marcello , Cuccia Liana , Gagliardotto Francesco , Magnano Carmelo , Caruso Vincenzo , Gerardi Calogera , Friscia Maria G. , Argento Crocetta , Campisi Saveria , Cantella Francesco , Cianciulli Paolo , Commendatore Francesca , D’Ascola Domenico G. , Fidone Carmelo , Filosa Aldo , Fragasso Alberto , Galati Marika , Giuffrida Gaetano , Giugno Roberto , Lombardo Turi , Malizia Roberto , Meo Anna , Rizzo Michele , Roccamo Gaetano , Romeo Maria A. , Violi Pietro , Pepe Alessia , D’Amico Gennaro , Morabito Alberto 
Published: October 2019

Three short-term randomised clinical trials suggested not difference of Deferiprone (L1) vs Deferoxamine (DFO) in term of iron overload efficacy in thalassemia major (TM) patients. To assess whether L1 (75mg/Kg) alone was comparable to a sequential treatment using L1 (75mg/Kg) for 4 days and DFO (50mg/Kg) for 3 days, we carried ahead a large long-term randomised clinical trial. One-hundred and forty consecutive patients with TM and serum ferritin between 1,500 and 3,000 ng/ml were randomly assigned to L1 (n°69) or sequential L1-DFO (n°71) and treated for 5 years. The main measure of efficacy was the reduction of serum ferritin levels. Secondary outcomes were liver and heart iron contents assessed by T2* magnetic resonance. After one year-treatment the mean serum feritin reduction was −105 ± 90.4 in L1 and −409 ± 64.2 in sequential L1-DFO treatment (p <0.01), respectively. The greater mean serum ferritin reduction of sequential L1- DFO treatment was also confirmed all over the study (2° year L1 106 ± 713, L1-DFO -321 ± 92 (p <0.01); 3° year L1 137 ± 137, L1-DFO -292 ± 117 (p <0.05); 4° year L1 216 ± 200, L1-DFO-230 ± 170 (p <0.01); 5° year L1 336 ± 244, L1-DFO -598 ± 203 (p <0.01)). After one-year treatment this sequential group showed greater efficacy in term of serum ferritin levels reduction (−409 ± 64.2) in comparison with the DFO alone arm (−232 ± 619) of a previous randomised multicenter clinical trial in which a comparable cohort of patients were studied (p<0.05). Reversible leukocytopenia was shown in 8 (11.5%) L1 and in 7 (9.8%) sequential L1-DFO treated patients. No agranulocythosis was reported on sequential L1-DFO treated patients during the 5 years study. Hypertransaminasemia developed in 13 (18.8%) L1 and in 5 (7%) sequential L1-DFO treated patients. No other major side effects have been reported. Discontinuation of treatment was necessary in 55.6% L1 and in 57.7% sequential L1-DFO treated patients (chi2 0.03, p=0.86). The failures of treatment were less in sequential L1-DFO arm (n°2) in comparison to L1 alone arm (n°8), although this difference not so far reached the statistical significance (chi2 3.4, p=0.06). These findings suggest that sequential L1-DFO treatment in a long-term study is more effective than L1 alone with milder and reversible side effects. Moreover, its efficacy is also higher in comparison with DFO alone at short-term evaluation.

Fig. 1 VARIATIONS OF THE FERRITIN LEVELS DURING FIVE YEARS TREATMENT BETWEEN THE TWO ARMS OF THE TRIAL Fig. 1. VARIATIONS OF THE FERRITIN LEVELS DURING FIVE YEARS TREATMENT BETWEEN THE TWO ARMS OF THE TRIAL