A study of magnetic resonance imaging assessment of cardiac and liver iron load in patients with haemoglobinopathies, myelodysplastic syndromes or other anaemias treated with deferasirox (the MILE study CICL670AAU01) - Results of an interim analysis at a planned sample size reassessment.

Background: Cardiac failure is the leading cause of death in patients with thalassaemia major. However, the introduction of new monitoring techniques, such as cardiac iron Magnetic Resonance Imaging (MRI), may lead to the improvement of patient care and prolong survival. Although the impact of cardiac siderosis in patients with thalassaemia major has been extensively studied, further examination of the effect of specific iron chelators such as deferasirox are important in the development of treatment protocols, while the clinical consequences of cardiac iron accumulation in patients with myelodysplastic syndromes (MDS) is still controversial. Aim(s): The primary objective of this study is to investigate the effect of single agent deferasirox on cardiac iron levels and cardiac function, in a cohort of patients receiving regular red blood cell transfusions. Method(s): Patients with transfusional siderosis were enrolled in this study and received deferasirox for 53 weeks. Doses up to 40 mg/kg/day were allowed according to transfusional requirement, response to chelation therapy and safety markers. Cardiac siderosis (cardiac T2* measured by linear fitting to the decay of logarithmic magnetic resonance signal) and left ventricular ejection fraction (LVEF) were measured at baseline and at 53 weeks. The sample size was originally calculated based on the standard deviation (SD) of the change in log(T2*) (0.47), according to previously published reports. A planned sample size reassessment as per protocol was undertaken when 42 patients had follow-up data. For the sample size reassessment, log(T2*) was calculated for each result and the change in log(T2*) estimated for each patient. Results from the interim sample size reassessment and the analysis of cardiac iron and function are described below. Result(s): Results were available for 36 patients with haemoglobinopathies (mainly represented by thalassaemia major), 5 patients with MDS and one post-bone marrow transplant patien