Abstract

Historically regularly transfused patients (pts) with Thalassemia Major (TM) have received prolonged infusions of subcutaneous deferroxamine (sc DFO) to prevent the lethal cardiac complications of transfusional hemosiderosis. Cardiac function is monitored with annual electrocardiograms (EKG) and 2 Dimensonial Doppler Echocardiogram (Echo). ICL670 (Exjade) is a newly identified oral iron chelator that has completed a one-year worldwide multicenter phase III clinical study of its safety and efficacy in comparison to sc DFO in TM. 17 TM pts in our institution participated in the Novartis ICL670-107 and 108 trials. They ranged in age from 2–36 years (yrs), the youngest being naive to chelation, five pts were previously noncompliant with the use of sc DFO, one of which developed acute heart failure more than 15 yrs prior to the study which resolved with vigorous DFO therapy and in whom all cardiac medications were discontinued 10 yrs prior to study entry. 10 TM pts ranging in age from 2–36 yrs received ICL670 at 10–30mg/kg/day and 7 TM pts ranging in age from 7–33 yrs received sc DFO at 40–60 mg/kg over 8 hour infusions 5 days per week. Each pt underwent a 2 dimensional Doppler Echo as part of their routine care prior to entry and after one year of study as well as regular EKGs before and during the study. Pre and post Liver Iron Concentration (LIC) was performed by biopsy in 15 adolescent/adult patients and 2 children had SQUID LIC. Laboratory analysis of blood counts, serum chemistries and ferritin levels were performed by a central laboratory. No clinically significant EKG changes were observed during the course of the study. Normal Ejection Fractions (EF) = 0.55 ± 0.75 ml/m2 and Shortening Fractions (SF) = >26%. One of the ten pts on ICL670 developed an abnormal EF = 47 and a SF = 24% compared to 0 of 7 pts on sc DFO. None of the pts experienced clinical cardiac decomensation. In conclusion regularly transfused TM pts receiving oral ICL670 for one year had no statistically significant mean changes or relative mean changes in EF or SF on 2 dimensional Dopler Echo in comparison to those pts receiving sc DFO.

Echo Results

 Mean Pre EF Mean Post EF Mean Change Mean Relative Change 
ICL670 60.3 ± 5.5 58.6 ± 5.4 −1.7 ± 6.9 −2% ± 12% 
DFO 63.7 ± 4.6 67.1 ± 4.2 3.4 ± 6.3 6% ± 11% 
 Mean Pre SF Mean Post SF Mean Change Mean Relative Change 
ICL670 32.4 ± 3.4 31.2 ± 3.3 −1.2 ± 4.3 −3% ± 13% 
DFO 35.0 ± 3.1 37.4 ± 3.3 2.4 ± 4.6 8% ± 14% 
 Mean Pre EF Mean Post EF Mean Change Mean Relative Change 
ICL670 60.3 ± 5.5 58.6 ± 5.4 −1.7 ± 6.9 −2% ± 12% 
DFO 63.7 ± 4.6 67.1 ± 4.2 3.4 ± 6.3 6% ± 11% 
 Mean Pre SF Mean Post SF Mean Change Mean Relative Change 
ICL670 32.4 ± 3.4 31.2 ± 3.3 −1.2 ± 4.3 −3% ± 13% 
DFO 35.0 ± 3.1 37.4 ± 3.3 2.4 ± 4.6 8% ± 14% 

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