Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload
Dudley J Pennell, John B Porter, Maria Domenica Cappellini, Lee Lee Chan, Amal El-Beshlawy, Yesim Aydinok, Hishamshah Ibrahim, Chi-Kong Li, Vip Viprakasit, Mohsen Saleh Elalfy, Antonis Kattamis, Gillian Smith, Dany Habr, Gabor Domokos, Bernard Roubert, Ali Taher, Dudley J Pennell, John B Porter, Maria Domenica Cappellini, Lee Lee Chan, Amal El-Beshlawy, Yesim Aydinok, Hishamshah Ibrahim, Chi-Kong Li, Vip Viprakasit, Mohsen Saleh Elalfy, Antonis Kattamis, Gillian Smith, Dany Habr, Gabor Domokos, Bernard Roubert, Ali Taher
Abstract
Background: The efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with β-thalassemia major in the cardiac sub-study of the EPIC trial.
Design and methods: Eligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years.
Results: Baseline myocardial T2* was severe (> 5 to < 10 ms) in 39 patients, and moderate-to-mild (10 to < 20 ms) in 62 patients. Mean deferasirox dose was 33.1 ± 3.7 mg/kg/d in the one-year core study increasing to 36.1 ± 7.7 mg/kg/d during the second year of treatment. Geometric mean myocardial T2* increased from a baseline of 11.2 to 14.8 ms at two years (P < 0.001). In patients with moderate-to-mild baseline T2*, an increase was seen from 14.7 to 20.1 ms, with normalization (≥ 20 ms) in 56.7% of patients. In those with severe cardiac iron overload at baseline, 42.9% improved to the moderate-to-mild group. The incidence of drug-related adverse events did not increase during the extension relative to the core study and included (≥ 5%) increased serum creatinine, rash and increased alanine aminotransferase.
Conclusions: Continuous treatment with deferasirox for two years with a target dose of 40 mg/kg/d continued to remove iron from the heart in patients with β-thalassemia major and mild, moderate and severe cardiac siderosis. (Clinicaltrials.gov identifier: NCT 00171821).
Trial registration: ClinicalTrials.gov NCT00171821.
Figures
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3012764/bin/9648.fig1.jpg)
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3012764/bin/9648.fig2.jpg)
Figure 3.
Changes in LVEF (mean ±…
Figure 3.
Changes in LVEF (mean ± SD) over two years in all patients (n=101)…
Figure 4.
Changes in LIC (mean ±…
Figure 4.
Changes in LIC (mean ± SD) over two years in all patients (n=101)…
Figure 5.
Changes in serum ferritin (median…
Figure 5.
Changes in serum ferritin (median ± 25 th /75 th percentiles) over two…
- In search of the optimal iron chelation therapy for patients with thalassemia major.Berdoukas V, Wood J. Berdoukas V, et al. Haematologica. 2011 Jan;96(1):5-8. doi: 10.3324/haematol.2010.034397. Haematologica. 2011. PMID: 21193427 Free PMC article. No abstract available.
- Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major.Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li CK, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Pennell DJ, et al. Haematologica. 2012 Jun;97(6):842-8. doi: 10.3324/haematol.2011.049957. Epub 2012 Jan 22. Haematologica. 2012. PMID: 22271905 Free PMC article. Clinical Trial.
- Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia.Pennell DJ, Porter JB, Cappellini MD, El-Beshlawy A, Chan LL, Aydinok Y, Elalfy MS, Sutcharitchan P, Li CK, Ibrahim H, Viprakasit V, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Pennell DJ, et al. Blood. 2010 Mar 25;115(12):2364-71. doi: 10.1182/blood-2009-04-217455. Epub 2009 Dec 8. Blood. 2010. PMID: 19996412 Clinical Trial.
- Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine.Pennell DJ, Porter JB, Piga A, Lai YR, El-Beshlawy A, Elalfy M, Yesilipek A, Kilinç Y, Habr D, Musallam KM, Shen J, Aydinok Y; CORDELIA study investigators. Pennell DJ, et al. Am J Hematol. 2015 Feb;90(2):91-6. doi: 10.1002/ajh.23876. Epub 2014 Nov 19. Am J Hematol. 2015. PMID: 25345697 Clinical Trial.
- A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA).Pennell DJ, Porter JB, Piga A, Lai Y, El-Beshlawy A, Belhoul KM, Elalfy M, Yesilipek A, Kilinç Y, Lawniczek T, Habr D, Weisskopf M, Zhang Y, Aydinok Y; CORDELIA study investigators. Pennell DJ, et al. Blood. 2014 Mar 6;123(10):1447-54. doi: 10.1182/blood-2013-04-497842. Epub 2014 Jan 2. Blood. 2014. PMID: 24385534 Free PMC article. Clinical Trial.
- Efficacy and safety of deferasirox in β-thalassemia major patients in Iran: a prospective study from a single referral center in Iran.Alavi S, Ebadi M, Ghazizadeh F, Arzanian MT, Shamsian B, Abdollah Gorji F. Alavi S, et al. Pediatr Hematol Oncol. 2014 Feb;31(1):76-86. doi: 10.3109/08880018.2013.861046. Epub 2014 Jan 2. Pediatr Hematol Oncol. 2014. PMID: 24383712 Clinical Trial.
- Electrophysiological properties and heart rate variability of patients with thalassemia major in Jakarta, Indonesia.Sukardi R, Wahidiyat PA, Gultom PA, Ikhsan M, Yamin M, Salim S, Djer MM. Sukardi R, et al. PLoS One. 2023 Jan 13;18(1):e0280401. doi: 10.1371/journal.pone.0280401. eCollection 2023. PLoS One. 2023. PMID: 36638135 Free PMC article.
- A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major.Khaled A, Salem HA, Ezzat DA, Seif HM, Rabee H. Khaled A, et al. Drug Des Devel Ther. 2019 Jul 22;13:2427-2436. doi: 10.2147/DDDT.S211630. eCollection 2019. Drug Des Devel Ther. 2019. PMID: 31413542 Free PMC article. Clinical Trial.
- Deferasirox: Over a Decade of Experience in Thalassemia.Moukalled NM, Bou-Fakhredin R, Taher AT. Moukalled NM, et al. Mediterr J Hematol Infect Dis. 2018 Nov 1;10(1):e2018066. doi: 10.4084/MJHID.2018.066. eCollection 2018. Mediterr J Hematol Infect Dis. 2018. PMID: 30416698 Free PMC article. Review.
- Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior.Ansari S, Azarkeivan A, Miri-Aliabad G, Yousefian S, Rostami T. Ansari S, et al. Caspian J Intern Med. 2017 Summer;8(3):159-164. doi: 10.22088/cjim.8.3.159. Caspian J Intern Med. 2017. PMID: 28932366 Free PMC article.
- Efficacy and Safety of Deferasirox in Pediatric Patients of Thalassemia at a Tertiary Care Teaching Hospital.Thakor DR, Desai CK, Kapadia JD, Dikshit RK, Mehariya KM. Thakor DR, et al. Indian J Med Paediatr Oncol. 2017 Apr-Jun;38(2):103-110. doi: 10.4103/ijmpo.ijmpo_103_16. Indian J Med Paediatr Oncol. 2017. PMID: 28900315 Free PMC article.
- Multicenter Study
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Benzoates / therapeutic use*
- Child
- Deferasirox
- Female
- Ferritins / blood
- Humans
- Iron / metabolism*
- Iron Chelating Agents / therapeutic use
- Iron Overload / chemically induced
- Iron Overload / drug therapy*
- Magnetic Resonance Imaging*
- Male
- Middle Aged
- Myocardium / pathology*
- Prognosis
- Prospective Studies
- Triazoles / therapeutic use*
- Ventricular Function, Left / drug effects*
- Young Adult
- beta-Thalassemia / complications
- beta-Thalassemia / drug therapy*
- Benzoates
- Iron Chelating Agents
- Triazoles
- Ferritins
- Iron
- Deferasirox
- ClinicalTrials.gov/NCT00171821
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![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3012764/bin/9648.fig3.jpg)
Figure 4.
Changes in LIC (mean ±…
Figure 4.
Changes in LIC (mean ± SD) over two years in all patients (n=101)…
Figure 5.
Changes in serum ferritin (median…
Figure 5.
Changes in serum ferritin (median ± 25 th /75 th percentiles) over two…
- In search of the optimal iron chelation therapy for patients with thalassemia major.Berdoukas V, Wood J. Berdoukas V, et al. Haematologica. 2011 Jan;96(1):5-8. doi: 10.3324/haematol.2010.034397. Haematologica. 2011. PMID: 21193427 Free PMC article. No abstract available.
- Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major.Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li CK, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Pennell DJ, et al. Haematologica. 2012 Jun;97(6):842-8. doi: 10.3324/haematol.2011.049957. Epub 2012 Jan 22. Haematologica. 2012. PMID: 22271905 Free PMC article. Clinical Trial.
- Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia.Pennell DJ, Porter JB, Cappellini MD, El-Beshlawy A, Chan LL, Aydinok Y, Elalfy MS, Sutcharitchan P, Li CK, Ibrahim H, Viprakasit V, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Pennell DJ, et al. Blood. 2010 Mar 25;115(12):2364-71. doi: 10.1182/blood-2009-04-217455. Epub 2009 Dec 8. Blood. 2010. PMID: 19996412 Clinical Trial.
- Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine.Pennell DJ, Porter JB, Piga A, Lai YR, El-Beshlawy A, Elalfy M, Yesilipek A, Kilinç Y, Habr D, Musallam KM, Shen J, Aydinok Y; CORDELIA study investigators. Pennell DJ, et al. Am J Hematol. 2015 Feb;90(2):91-6. doi: 10.1002/ajh.23876. Epub 2014 Nov 19. Am J Hematol. 2015. PMID: 25345697 Clinical Trial.
- A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA).Pennell DJ, Porter JB, Piga A, Lai Y, El-Beshlawy A, Belhoul KM, Elalfy M, Yesilipek A, Kilinç Y, Lawniczek T, Habr D, Weisskopf M, Zhang Y, Aydinok Y; CORDELIA study investigators. Pennell DJ, et al. Blood. 2014 Mar 6;123(10):1447-54. doi: 10.1182/blood-2013-04-497842. Epub 2014 Jan 2. Blood. 2014. PMID: 24385534 Free PMC article. Clinical Trial.
- Efficacy and safety of deferasirox in β-thalassemia major patients in Iran: a prospective study from a single referral center in Iran.Alavi S, Ebadi M, Ghazizadeh F, Arzanian MT, Shamsian B, Abdollah Gorji F. Alavi S, et al. Pediatr Hematol Oncol. 2014 Feb;31(1):76-86. doi: 10.3109/08880018.2013.861046. Epub 2014 Jan 2. Pediatr Hematol Oncol. 2014. PMID: 24383712 Clinical Trial.
- Electrophysiological properties and heart rate variability of patients with thalassemia major in Jakarta, Indonesia.Sukardi R, Wahidiyat PA, Gultom PA, Ikhsan M, Yamin M, Salim S, Djer MM. Sukardi R, et al. PLoS One. 2023 Jan 13;18(1):e0280401. doi: 10.1371/journal.pone.0280401. eCollection 2023. PLoS One. 2023. PMID: 36638135 Free PMC article.
- A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major.Khaled A, Salem HA, Ezzat DA, Seif HM, Rabee H. Khaled A, et al. Drug Des Devel Ther. 2019 Jul 22;13:2427-2436. doi: 10.2147/DDDT.S211630. eCollection 2019. Drug Des Devel Ther. 2019. PMID: 31413542 Free PMC article. Clinical Trial.
- Deferasirox: Over a Decade of Experience in Thalassemia.Moukalled NM, Bou-Fakhredin R, Taher AT. Moukalled NM, et al. Mediterr J Hematol Infect Dis. 2018 Nov 1;10(1):e2018066. doi: 10.4084/MJHID.2018.066. eCollection 2018. Mediterr J Hematol Infect Dis. 2018. PMID: 30416698 Free PMC article. Review.
- Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior.Ansari S, Azarkeivan A, Miri-Aliabad G, Yousefian S, Rostami T. Ansari S, et al. Caspian J Intern Med. 2017 Summer;8(3):159-164. doi: 10.22088/cjim.8.3.159. Caspian J Intern Med. 2017. PMID: 28932366 Free PMC article.
- Efficacy and Safety of Deferasirox in Pediatric Patients of Thalassemia at a Tertiary Care Teaching Hospital.Thakor DR, Desai CK, Kapadia JD, Dikshit RK, Mehariya KM. Thakor DR, et al. Indian J Med Paediatr Oncol. 2017 Apr-Jun;38(2):103-110. doi: 10.4103/ijmpo.ijmpo_103_16. Indian J Med Paediatr Oncol. 2017. PMID: 28900315 Free PMC article.
- Multicenter Study
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Benzoates / therapeutic use*
- Child
- Deferasirox
- Female
- Ferritins / blood
- Humans
- Iron / metabolism*
- Iron Chelating Agents / therapeutic use
- Iron Overload / chemically induced
- Iron Overload / drug therapy*
- Magnetic Resonance Imaging*
- Male
- Middle Aged
- Myocardium / pathology*
- Prognosis
- Prospective Studies
- Triazoles / therapeutic use*
- Ventricular Function, Left / drug effects*
- Young Adult
- beta-Thalassemia / complications
- beta-Thalassemia / drug therapy*
- Benzoates
- Iron Chelating Agents
- Triazoles
- Ferritins
- Iron
- Deferasirox
- ClinicalTrials.gov/NCT00171821
![Figure 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3012764/bin/9648.fig4.jpg)
Figure 5.
Changes in serum ferritin (median…
Figure 5.
Changes in serum ferritin (median ± 25 th /75 th percentiles) over two…
![Figure 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3012764/bin/9648.fig5.jpg)
Source: PubMed