Efficacy and Safety of Deferasirox for Reducing Total Body and Cardiac Iron in Thalassemia.

ABSTRACT

Objective: To assess the efficacy of deferasirox as an iron chelator, with specific reference to reducing cardiac iron overload. Design: Prospective, open label, single arm study between 2008- 2010. Setup Thalassemia center at a teaching hospital. Participants: 30 multitransfused Thalassemia Major (TM) patients receiving deferasirox (DFX) therapy. Methods: All patients had MRI T2*evaluation for cardiac iron load before starting DFX therapy. MRI T2* was performed on a 1.5 tesla Siemens sonata machine using thalassemia tools software and the ejection fraction measured using standard cardiac magnetic resonance sequence. Quantification of cardiac iron deposit was categorized into T2* <10 ms as high cardiac risk, 10- 20 ms as intermediate risk, and >20 ms as low risk. We also estimated left ventricular ejection fraction (LVEF), end systolic volume (ESV) and end diastolic volume (EDV) using standard sequence. EF <56 % was considered to be significant cardiac dysfunction. DFX was administered in an initial dose of 20mg/kg/ day and increased to a maximum of 35mg/kg/day. Serum ferritin level was estimated in pretransfusion samples at 1-3 monthly intervals. The primary end point of the study was change in serum ferritin level and cardiac MRI T2* value after 12-18 months therapy. Results: Of the 30 patients, cardiac iron value of >20 ms was seen in 15 (50%), whereas 9 (30% ) had 20-10 ms, and 6 (20% ) had ≤10 ms. The mean serum ferritin pre DFX therapy of all cases was 3859.8 ± 1690.70 ng/mL (1066 – 6725 ng/mL) and mean cardiac T2* was 23.8±15.2 ms (6.24-69.2 ms). After 12 to 18 months of DFX therapy on a mean dose of 33 mg/kg/day, the mean serum ferritin was 2693.4 ±1831.5 ng/mL (drop by 30.2%, P<0.001) and mean cardiac T2* was 24.2±12.9 ms (increase of 1.6 %, P=0.87). Percentage change in cardiac iron was greater in high risk (24.8%) and intermediate risk (33.4%) patients than low risk patients (8.4%), though these values were not statistically significant. LVEF was 62.0 (±7.0%) before treatment and changed to 58.9 (± 4.8%) after 18 months of therapy but the values remained within normal range and this change was not significant (P=0.061). Adverse effect of DFX included diarrhea, maculopapular skin rash and transient proteinuria that necessitated temporary stoppage of medication. Conclusion: Deferasirox monotherapy has a good safety profile and effectively chelates total body iron. It is also a good myocardial iron chelator, more efficacious in moderate to severe cardiac iron overloaded patients.