Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST)

Pediatr Blood Cancer. 2017 Sep;64(9). doi: 10.1002/pbc.26507. Epub 2017 Mar 10.

Abstract

Background: Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years.

Procedure: Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study. Patients aged 2 to less than 6 years at enrollment received deferasirox according to local prescribing information, with the primary objective of evaluating safety, specifically renal and hepatic function. Serum ferritin was observed as a surrogate efficacy parameter.

Results: In total, 267 patients (mean age 3.2 years) predominantly with β-thalassemia (n = 176, 65.9%) were enrolled. Mean ± standard deviation deferasirox dose was 25.8 ± 6.5 mg/kg per day over a median of 59.9 months. A total of 145 patients (54.3%) completed 5 years' treatment. The proportion of patients with two or more consecutive postbaseline measurements (≥7 days apart) of serum creatinine higher than age-adjusted upper limit of normal (ULN) and alanine aminotransferase more than five times the ULN was 4.4% (95% confidence interval [CI]: 2.1-7.9) and 4.0% (95% CI: 1.8-7.4), respectively. Median serum ferritin decreased from 1,702 ng/ml at baseline to 1,127 ng/ml at 5 years. There were no new safety signals.

Conclusions: Safety and efficacy of deferasirox in young pediatric patients in this long-term, observational study in everyday clinical practice were consistent with the known deferasirox profile.

Keywords: deferasirox; hemosiderosis; iron chelation; iron overload; pediatric; real world.

Publication types

  • Observational Study

MeSH terms

  • Benzoates / therapeutic use*
  • Chelation Therapy / methods
  • Child, Preschool
  • Deferasirox
  • Female
  • Hematologic Diseases / therapy
  • Hemosiderosis / drug therapy*
  • Hemosiderosis / etiology
  • Humans
  • Iron Chelating Agents / therapeutic use*
  • Male
  • Transfusion Reaction*
  • Triazoles / therapeutic use*

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Deferasirox