Efficacy and safety of deferasirox for reducing total body and cardiac iron in thalassemia.

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 T2evaluation 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.