Two Studies Look at Cardiac Iron Removal with Exjade
July 22, 2010 – Two recent studies examine the efficacy of the oral chelator deferasirox (Exjade) in reducing cardiac iron in patients with thalassemia.
| Authors of “Efficacy of deferasirox in reducing and preventing cardiac iron overload in β- thalassemia”
Dudley J. Pennell, John B. Porter, Maria Domenica Cappellini, Amal El-Beshlawy, Lee Lee Chan, Yesim Aydinok, Mohsen Saleh Elalfy, Pranee Sutcharitchan, Chi-Kong Li, Hishamshah Ibrahim, Vip Viprakasit, Antonis Kattamis, Gillian Smith, Dany Habr, Gabor Domokos, Bernard Roubert, and Ali Taher |
“Efficacy of deferasirox in reducing and preventing cardiac iron overload in β-thalassemia”, published in the March 25, 2010 volume of the journal Blood, relates the results of a one-year prospective, multicenter trial involving 192 patients. The patients were divided into two arms: the cardiac iron reduction arm and the prevention arm. The cardiac prevention arm included 114 patients whose T2*, liver iron concentration and ferritin measurements indicated the possibility of cardiac issues. The prevention arm included 78 patients whose measurements indicated a more typical cardiac health profile.
Patients in both arms were treated with deferasirox. The results after one year were as follows:
· In the cardiac iron reduction arm, T2* measurements improved from a baseline of 11.2 (+/- 40.5%) to 12.9 (+/ 49.5%), an improvement of 16%. LVEF (left ventricular ejection fraction) was unchanged.
· In the prevention arm, T2* measurements were unchanged, and LVEF showed a 1.8% increase.
· In both arms, there was an overall decrease in LIC and ferritin levels, although 17% of patients in the cardiac iron reduction arm and 20% of those in the prevention arm saw an increase in ferritins.
The authors summarize their results by stating that “deferasirox treatment for 1 year removed iron from the heart and maintained LVEF in patients with β-thalassemia with mild, moderate and severe myocardial siderosis [editor’s note: Patients with the worst cardiac iron overload, T2*<5 msec, were not included in this study]. In patients with normal myocardial iron levels, deferasirox maintained myocardial iron levels and improved LVEF.”
| Authors of “The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores”
John C. Wood, Barinder P. Kang, Alexis Thompson, Patricia Giardina, PaulHarmatz, Tara Glynos, Carole Paley, and Thomas D. Coates |
The second study, “The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores” has been prepublished online ahead of print in the journal Blood. This prospective, multicenter, open-label, single-arm study examines the response of cardiac and liver iron to deferasirox therapy for 18 months. Twenty-eight patients were enrolled; one withdrew prior to commencement, leaving 27 in the intent to treat population. Of the 27 patients, 22 completed the trial. All patients in the study had abnormal T2* and normal LVEF. The results of this trial include:
· In the 22 patients completing the trial, LIC improvement was 16% and T2* improvement was 14%. Changes in LIC and T2* were significant at the 6-month and 12-month points, but were no longer significant at 18 months.
· Cardiac iron improved by 24% in patients having LIC in the lower two quartiles (lower LIC) and worsened by 8.7% in patients having LIC in the upper two quartiles (higher LIC).
· 13 patients saw cardiac improvement; the remaining participants saw their T2* scores worsen. The reason for this second set of patients being non-responsive to the drug cannot be definitely ascertained; however, it seems likely that inadequate compliance may be a significant factor.
· LVEF was unchanged at all time points.
· The authors conclude that “monotherapy with deferasirox was effective in patients with mild-to-moderate iron stores but failed to remove cardiac iron in patients with severe hepatic iron burdens.”
When discussing the trial, the authors state that “the most striking observation was the clear demarcation between responders and non-responders…patients having severe hepatic iron overload may warrant more aggressive therapy if the therapeutic goal is rapid cardiac iron clearance, the patient already has severe cardiac iron deposition, the patient is known to be noncompliant, or facilities for monitoring cardiac iron and cardiac function are limited or unavailable.”
The authors also state that “cardiac iron clearance was also a powerful function of final LIC, sharply increasing as LIC approached normal levels…The simplest explanation is that iron chelation with deferasirox is a competitive process, with cardiac effectiveness improving once liver iron is depleted.”
| True or False? If you have low ferritin levels, you don’t need to have a T2* measurement. | |
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False. Sometimes a person can have cardiac iron even if his/her ferritins are low. It’s a good idea to include T2* as part of your annual comprehensive care exam so you and your team have a better picture of the iron in your body. |
“These two important studies expand the medical literature about issues that many clinicians and patients may have already learned about how to use deferasirox (Exjade),” says CAF Medical Advisory Board Chair Ellis Neufeld. “Both studies focus on patients with elevated cardiac iron levels, or on preventing elevated iron in the heart, as assessed by cardiac MRI T2*.
“While many patients with moderate heart iron by MRI (T2* between 8 and 20 msec) can have successful lowering of cardiac iron (rise in T2*), deferasirox is probably NOT the optimal treatment in patients with the worst cardiac iron levels (patients with T2* lower than 5 msec weren’t tested in the first study mentioned above, and those with levels below 6 msec didn’t respond in the second study). Such patients should talk to their hematologist about using continuous deferoxamine, perhaps in combination with deferiprone. Achieving the best results with deferasirox may require high doses in some individuals, and even with higher doses, a fraction of patients don’t respond at all.”
If you would like more information, please contact CAF at info@cooleysanemia.org.