ALBERT

Description: Abstract 2125 Background: Young children typically receive more blood transfusions per kg body weight compared with adults, increasing the risk of iron overload. Iron overload may lead to endocrine abnormalities that can affect growth and development. Data from clinical trials of the iron chelator deferasirox (Exjade®) have demonstrated tolerability and efficacy in transfused patients with a range of underlying anemias. The registration clinical trials included 52 patients aged 2–33% increase from baseline on two consecutive measurements (baseline range 20–39 μmol/L); none of these five patients discontinued. Increased ALT 〉5 × ULN was confirmed in 11/247 patients (4.5%); most abnormalities were transient, five of these patients discontinued (increased ALT [n=3], protocol deviation [n=1] and vomiting [n=1]). The most common (≥4 patients) investigator-reported drug-related AEs were investigations and GI disorders; these are shown in the Table as investigator-reported preferred terms. The majority of investigations were mild-to-moderate in severity. Overall, 178/247 patients (72.1%) are continuing the study. Main reasons for discontinuation were protocol deviation (n=12, 4.9%) and AEs (n=7, 2.8%: increased ALT; proteinuria; hepatic AE [increased ALT/AST for second time after drug administration]; abdominal pain/vomiting/hypokalemia/transaminase elevation; vomiting; reversible increase of ALT of 239 U/L reported as hepatic cytolysis; transaminase elevation/lack of efficacy; all n=1). One patient with DBA died (severe pancytopenia and sepsis following bone marrow transplantation). Conclusions: The safety profile of deferasirox in very young pediatric patients was consistent with the available evidence in adult patients, including the rate of creatinine and liver enzyme changes which did not appear to be progressive. Many patients did not have appropriate dose adjustments during the study, despite substantial increases in weight. In addition to safety and efficacy parameters, weight change in pediatric patients should be considered during dose adjustments to optimize efficacy and safety. Disclosures: Vichinsky: Novartis: Consultancy, Research Funding; ApoPharma: Consultancy, Research Funding; ARUP Research lab: Research Funding. Bernaudin:Novartis: Research Funding. El-Ali:Novartis: Employment. Arrowsmith:Novartis: Employment. Martin:Novartis: Employment.