Deferasirox (Exjade®) Significantly Improves Cardiac T2* in Heavily Iron-Overloaded Patients with β-Thalassemia Major

Abstract

Introduction: Iron overload currently remains a major cause of morbidity and mortality in patients (pts) with thalassemia major (TM), despite the availability of iron chelation therapy. Magnetic resonance imaging (MRI) can be used to measure tissue iron levels and identify pts with iron overload. The aim of this study was to monitor cardiac siderosis using MRI T2* in a cohort of Omani pts with TM.Methods: Cardiac MRI T2* was assessed in 19 pts enrolled at a single center in Oman. All pts had transfusional iron overload and had received chelation therapy (16/19 pts DFO + deferiprone; 2/19 DFO; 1/19 deferiprone) prior to enrollment in the ESCALATOR study. After completing a 1-year core phase of the ESCALATOR study, cardiac iron was evaluated as part of the site standard of care. Hence, pts had been receiving once-daily oral deferasirox starting with 20 mg/kg/day with subsequent dose adjustments for 12 months prior to the first cardiac T2* assessment (baseline [BL]). Pts continued on deferasirox throughout the 18-month period of this present evaluation.Results: All 19 pts (11 male; 8 female) completed 18 months of evaluation. Mean age (±SD) was 18 years (±4.5; range 10–29). At BL, pts had a mean cardiac T2* (±SD) of 17.2 (±10.8) ms (table) indicative of cardiac iron loading, (normal >20 ms) and a high median BL serum ferritin (SF) of 5497 ng/mL, signifying a high total body iron burden (r = −0.35). Pts also had a high liver iron concentration (LIC), which was correlated with both BL cardiac T2* and SF levels (r = −0.52 and 0.53, respectively). When the data were analyzed by BL cardiac T2* subgroups (<10 ms [n=6], 10–20 ms [n=7], <20 ms [n=13] and >20 ms [n=6]), all subgroups demonstrated a high BL SF. Mean deferasirox dose (±SD) in all pts was 25.9 (±2.3) mg/kg/day at BL, 32.0 (±4.4) mg/kg/day at 6 months and 37.7 (±5.5) mg/kg/day at 18 months, with dose adjustments carried out as per ESCALATOR study protocol.Overall, deferasirox significantly improved mean cardiac T2* by 3.6 and 4.3 ms at 6 (P=0.007) and 18 months (P=0.02), respectively. Further analysis showed a significant improvement in T2* (P<0.05) at 18 months in all subgroups except those pts with normal BL T2* (>20 ms), who only showed an improvement at 6 months. Moreover, deferasirox significantly reduced SF (P=0.001) and LIC (P=0.01) in the total study population at 18 months. Additional subgroup analyses for the changes at 6 and 18 months relative to BL are shown in the table.Table. Efficacy of deferasirox after 6 and 18 months of therapyAll pts (n=19)<10 ms (n=6)10–20 ms (n=7)<20 ms (n=13)>20 ms (n=6)Mean cardiac T2*, ms (±SD)BL17.2 (10.8)6.3 (2.2)14.9 (3.1)10.9 (5.2)30.8 (5.1)6 months20.8 (13.7)‡6.2 (2.6)19.2 (6.8)13.2 (8.5)37.2 (4.9)‡18 months21.5 (12.8)‡7.8 (3.2)‡21.4 (8.7)‡15.1 (9.6) ‡35.2 (6.0)Median SF, ng/mLBL549763855497549747336 months41286100480348033031‡18 months4235‡593746554674‡1793‡Mean LIC, mg/g dw (±SD)Pre-BL†24.17 (8.96)29.57 (11.21)24.81 (7.69)27.01 (9.38)18.02 (3.44)6 months19.71 (11.42)‡25.23 (10.73)23.34 (11.16)24.22 (10.55)9.93 (5.89)‡18 months17.62 (12.93)‡20.02 (10.85)23.97 (13.96)22.15 (12.28)7.82 (8.50)‡†These values were measured 6 months prior to BL T2* MRI; ‡significantly improved (P<0.05) compared with BLConclusions: Deferasirox therapy significantly improved cardiac T2* in these heavily iron-overloaded pts with TM. Improvement was seen in pts with various degrees of cardiac siderosis, including those pts with BL cardiac T2* <10 ms, indicative of high cardiac iron burden. SF and LIC were also significantly reduced in all pts, indicating that deferasirox reduced both cardiac and total body iron burden in these pts. That deferasirox dose was increased in all pts over the 18 months of the study highlights the importance of dose titration to achieve treatment goals.