S120: RANDOMIZED CONTROLLED TRIAL OF THE EFFICACY AND SAFETY OF DEFERIPRONE: SUBGROUP ANALYSIS OF PEDIATRIC PATIENTS IN IRON-OVERLOADED PATIENTS WITH SICKLE CELL DISEASE AND OTHER ANEMIAS

Abstract

Background: Children with sickle cell disease (SCD) managed with blood transfusions often require iron chelation therapy to prevent iron overload.1 Deferoxamine (DFO) is an iron chelator approved for pediatrics that is often infused; however, adherence is a key challenge due to the burdensome route of administration.2 Deferiprone (DFP), an oral iron chelator, is a first-line treatment for transfusional iron overload in children and adults with SCD and other anemias.3 DFP is noninferior to DFO in SCD with iron overload (evaluated by liver iron concentration [LIC]) and has an acceptable safety profile.4 This subgroup analysis of FIRST (NCT02041299) assessed whether efficacy and safety of DFP were comparable to DFO in children with SCD. Methods: In this phase 4 open-label study, patients were randomized 2:1 to DFP or DFO for 12 months. The subgroup analysis included children (2–16 years of age) with SCD or another rare anemia treated for transfusional iron overload. Children received either oral DFP three times a day or subcutaneous DFO infusion 5–7 days a week. Iron load was monitored and dosage adjustments were allowed. The primary endpoint was change in LIC from baseline to month 12. Data were analyzed for all patients with a baseline and a follow-up LIC assessment (efficacy population). Safety assessments were done for all patients who received at least 1 dose of study drug (safety population). All patients provided informed consent or assent. Results: Of 228 patients in the safety population, 128 (DFP, n=86; DFO, n=42) were children. Most children (DFP, 75.6%; DFO, 80.9%) had a primary diagnosis of SCD (HbS). Mean ages (SD) in the DFP and DFO groups were 9.9 (3.7) and 10.9 (3.0) years (P=0.09), respectively. There were no significant differences between the DFP and DFO groups in sex (males, 59.3% vs 57.1%; P=0.85), ethnicity (P=0.68), or race (P=0.34). 5 children withdrew due to AEs (all DFP) and 19 withdrew for other reasons (DFP, n=14; DFO, n=5). There was not a significant difference in number of withdraws between groups (P=0.23). Children treated with DFP or DFO showed no significant differences in overall incidence of AEs (P=0.77; including neutropenias [P=0.30]), severe AEs (P=0.10), serious AEs (P=0.16), or withdrawals due to AEs (P=0.17). A difference in overall incidence of nonserious AEs considered at least possibly related to DFP (59.3% vs 33.3%; P=0.01) was found. For AEs ≥5%: see Table 1. The only AE with a significantly higher rate with DFP vs DFO was elevated liver enzymes (P=0.03)—a known transient reaction to DFP typically resolving with continued DFP. There were no AEs observed with DFP that had not been previously reported. One child developed agranulocytosis during parvovirus infection, which resolved the following day; and children <6 years of age receiving DFP had a comparable safety profile to older children (6–16 years of age) receiving DFP. In the efficacy population, after 12 months, there was no significant difference in mean (SD) LIC change from baseline with DFP vs DFO (-3.39±4.24 mg/g vs -2.99±3.16 mg/g, respectively; P=0.57). Conclusions: This subgroup analysis of children receiving chronic transfusions for SCD or other anemias corroborates previous findings that DFP is comparable to DFO in reducing LIC. No new safety concerns were observed. These findings may benefit children and healthcare providers when considering effective iron chelation therapy that may also address treatment-adherence concerns.