Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up

Abstract

Patients with ␤-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged > 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received > 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with > 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ؎ 11.2 mg Fe/g dry weight (dw; n ‫؍‬ 103; P < .001) and 3.1 ؎ 7.9 mg Fe/g dw (n ‫؍‬ 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n ‫؍‬ 196; P < .001) and 371 ng/mL (n ‫؍‬ 147; P < .001), respectively, after > 4 years' exposure. Investigator-assessed, drugrelated adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with ␤-thalassemia suggests treatment for < 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials-.gov as #NCT00171210. (Blood. 2011; 118(4):884-893)

Sustained improvements in myocardial T2* over 2 years in severely iron‐overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine

“…The long-term safety profile of deferasirox was consistent with previous reports [7,27], with the most common drug-related AEs being increased laboratory parameters. Although patients received intensified dosing regimens for deferasirox and DFO, there was no impact on the AE profile, supporting the positive risk-benefit ratio of highdose therapy for patients with high myocardial and/or hepatic iron burden, as recommended in the Thalassaemia International Federation guidelines [28].…”

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

“…It is predicted that these oral medications should provide better overall outcome with chelation therapy compared with DFO due to their ease of use with better compliance [17,18]. Deferasirox, a once-daily oral chelator, showed efficacy with an acceptable safety profile in adult and pediatric populations with up-to 5-year follow up in a large scale prospective clinical studies [19]. However, cost related to this new oral chelator remains the major obstacle for many developing countries for their patients to get access for this medication.…”

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

“…[22][23][24][25][26][27][28] However, data regarding the use of deferasirox after allogeneic HSCT are limited. 15,17,19,20 This prospective multicenter trial is, to the best of our knowledge, the largest trial evaluating the efficacy and safety of deferasirox after allogeneic HSCT.…”