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

Patients with beta-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 be-cause 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, drug-related adverse events, including increased blood creatinine (11.2%), ab-dominal 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 beta-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)