Long-Term Treatment with the Once-Daily Oral Iron Chelator Deferasirox (Exjadereg], ICL670) Is Effective and Generally Well Tolerated in Pediatric Patients.
Authors: Piga A. , Bejaoui M. , Kilinc Y. , Perrotta S. , Vichinsky E. , Arrowsmith-Bensasson C. , Glimm E. , Alberti D. 
Published: October 2019

Abstract
Introduction: A large proportion of pts enrolled in the deferasirox clinical trials were children aged 2–<16 years. Data from the core, 1-year trials demonstrated that deferasirox was effective in these pts, with a similar safety profile to adults. After the core trials, pts entered 4-year extension phases. This post-hoc analysis presents long-term deferasirox safety and efficacy data in pediatric pts.
Methods: Pediatric pts with various underlying anemias (β-thalassemia, sickle cell disease, other congenital anemias) either received deferasirox in the core trials (deferasirox cohort) or crossed over from deferoxamine to deferasirox during the extension phases (crossover cohort). Safety and efficacy were assessed monthly, primarily by evaluating the incidence and type of adverse events (AEs) and by measuring serum ferritin (SF) levels. Liver iron concentration (LIC) was measured at baseline and the end of the core trials.
Results: The deferasirox (n=289) and crossover (n=144) cohorts have been receiving deferasirox for a median of 2.6 and 1.6 years, respectively. Pediatric subgroups were 2–<6 (n=70), 6–<12 (n=192) and 12–<16 (n=171) years. During the core trials, changes in SF and LIC with deferasirox were well correlated (data not shown). Median SF levels decreased in pts receiving deferasirox 30 mg/kg/day and were maintained in pts receiving 20 mg/kg/day (Table). SF levels initially increased in pts receiving 5 and 10 mg/kg/day, although dose escalation generally resulted in a decrease, with levels falling below baseline at data cut-off.
Median absolute SF values (ng/mL) in the deferasirox cohort Initial dose, mg/kg/day All (n=289) 5 and 10 (n=129) 20 (n=87) 30 (n=73) *Dose modification to most appropriate dose Baseline 2409 2126 2504 3400 Wk 52* 2648 2772 2296 2632 Wk 128 1847 1963 2232 1750
SF levels in the crossover cohort remained stable during deferasirox therapy (mean dose 21.0 mg/kg/day). In total, 392 (90.5%) pediatric pts continue to receive deferasirox. Of the 41 discontinuations, 21 were due to AEs. There were two deaths; both were in the deferasirox cohort and considered by the Program Safety Board to be unrelated to treatment (one was considered possibly related by the investigator). The most common drug-related AEs were mild, transient diarrhea and vomiting (both n=19, 4.4%), abdominal pain and nausea (both n=17, 3.9%), and mild/moderate skin rash (n=24, 5.5%). There were no progressive increases in markers of liver or renal function. There were rare cases of lens opacities and high-frequency hearing loss of uncertain clinical significance. The incidence and pattern of AEs was similar in all pediatric pts, including those aged <6 years. Physical and sexual development proceeded normally in all pts.
Conclusions: These pediatric pts had high baseline iron burden, indicating an increased risk of iron overload-related complications. Treatment with deferasirox for up to 2.6 years led to a clinically relevant, continuous reduction in SF levels. Changes were dose dependent; 20 and 30 mg/kg/day effectively maintained or reduced body iron stores, respectively. Long-term deferasirox treatment was generally well tolerated in pediatric pts, with a safety profile comparable to that in adults over a similar period.