A 5-Years Follow-up in Deferasirox Treatment: Improvement of Cardiac and Hepatic Iron Overload and Amelioration in Cardiac Function in Thalassemia Major Patients
Authors: Cassinerio Elena , Roghi Alberto , Orofino Nicola , Pedrotti Patrizia , Zanaboni Laura , Poggiali Erika , Giuditta Marianna , Consonni Dario , Cappellini Maria Domenica 
Published: November 2019

Abstract
Introduction. During the last 10 years the cardiac deaths in adult thalassemia major (TM) patients are significantly reduced because of the availability of new oral iron chelators and the introduction of T2* cardiovascular magnetic resonance (CMR), which allows to evaluate the cardiac iron load. Deferasirox (DFX) is an oral iron chelator with established efficacy and safety. Based on myocardial T2* values, the risk of cardiac heart failure can be estimated prompting to intensify chelation therapy, if necessary. We would evaluate by T2* CMR the efficacy of DFX in preventing and removing cardiac and hepatic iron load and cardiac volume changes, along 5 years in adult TM patients.
Methods. Twenty-three TM patients (9 males/14 women, mean age 36 ± 4 yrs) were included in this study. They repeated CMR to assess myocardial and liver iron load. Cardiac and hepatic iron load was assessed measuring myocardial T2* at 3 different time-points: basal value (t0), after a period of 2.5 years ± 6 months (t1) and after a period of five years (t2). During the follow-up period two patients became pregnant and they stopped chelation therapy with deferasirox for the duration of the pregnancy: they restarted oral iron chelation therapy with DFX after the delivery without any adverse event. Six patients underwent treatment with interferon and ribavirin to treat their hepatitis C: the dose of DFX was modulated based on increased iron intake during the treatment period.
Results. Overall, the mean iron intake was 0.34±0.10 mg/Kg/day and the pre-transfusional mean hemoglobin (Hb) was 9.7±0.5 g/dl. The median ferritin value was 575 ng/ml (range 252-2530 ng/ml). The mean dosage of deferasirox at the beginning of the observation period was 24.4 ± 5.3 mg/kg/day; the mean dose of DFX along the 5-years follow-up was 25.3 ± 1.2 mg/kg/day. An initial reduction of mean ferritin levels was observed in the first 2.5 years of observation reaching a statistical significance only after 5 years (1055±563 ng/ml at baseline vs 960±568 ng/ml at t1 vs 751±627 ng/ml at t2, p=0.009 between t1 and t2). Myocardial T2* values changed progressively and increased significantly between t0 and t2 (t0: 27.15 ± 9.58 vs t2: 36.64 ± 6.68, p=0.0001). At baseline evaluation, a cardiac T2* value < 20 ms was detected in 6 patients (26 %): they showed an improvement of cardiac T2* values between t0 and t1, with normal T2* levels reached in all patients at t2. In the overall population a significant reduction of both end-diastolic and end-systolic left ventricular volumes (EDV, ESV) were detected between t0 and t2 (EDV, t0: 132±31 ml vs t2: 124±22 ml, p=0.033; ESV, t0: 48±14 ml vs t2: 41±10 ml, p=0.0007) (Table 1). A significant reduction in Liver Iron Concentration (LIC) was detected at t1 (5.36±3.58 mg/g dw at baseline vs 3.35±2.68 mg/g dw at t1, p=0.004). In patients with cardiac iron overload at baseline (n.6), mean cardiac T2* values doubled at t2 and mean LIC value is reduced of 29 %.
Conclusions. Wecan conclude that DFX, at a personalized dose, progressively and significantly reduces myocardial and liver iron overload and it prevented the iron deposition along 5-years of continuous treatment.
Table 1. Left ventricular ejection fraction and cardiac volumes during the period of follow-up. Overall patients Patients with baseline T2* 10–20 ms t0 t2 P-value t0 t2 P-value LVEF (%, mean ± SD) 64 ± 6 66 ± 6 ns 61 ± 7 63 ± 6 Ns EDV (ml, mean ± SD) (nv: 52-141 ml) 132 ± 31 124 ± 22 0,033 139 ± 33 121 ± 22 0.03 ESV (ml, mean ± SD) (nv: 13-51 ml) 48 ± 14 41 ± 10 0,0007 54 ± 14 44 ± 10 0.02
LVEF: Left Ventricular Ejection Fraction; EDV: End-Diastolic left ventricular Volume; nv: normal value; ESV End-Systolic left ventricular Volume; SD: Standard Deviation; ns: not significative.

Disclosures
Cappellini: Novartis, Shire, Cellgene, Sanofi: Advisory board Other.