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

Deferiprone (DFP), an oral iron chelator, has recently been approved as the first-line treatment for transfusional iron overload in pediatric and adult patients with Sickle Cell Disease (SCD) and other anemias. The FIRST study (NCT02041299) reported that DFP is noninferior to Deferoxamine (DFO) in patients with SCD and iron overload (as assessed by Liver Iron Concentration [LIC]) and has an acceptable safety profile. Here, we report a subgroup analysis of FIRST to assess whether the efficacy and safety of DFP are comparable to DFO in children with SCD. In this multicenter, 2-arm, randomized, open-label study, eligible patients were randomized 2:1 to receive DFP or DFO for 12 months. The subgroup analysis included children (2–16 years of age) with SCD or another rare anemia who were treated for transfusional iron overload. The primary efficacy endpoint was the change in LIC from baseline to month 12. Safety was assessed by Adverse Events (AEs) in the study period. The safety analysis was composed of 128 (DFP, n = 86; DFO, n = 42) children; most (DFP, 76%; DFO, 81%) had a primary diagnosis of SCD (HbS). Mean age (SD) in the DFP and DFO arms were 9.9 (3.7) and 10.9 (3.0) years (p = 0.09), respectively. 5 children in the DFP arm withdrew due to AEs and 19 (DFP, n = 14; DFO, n = 5) for other reasons. Children treated with DFP or DFO showed no difference in the number of AEs (p = 0.77; including neutropenia [p = 0.30]), severe AEs (p = 0.10), serious AEs (p = 0.16), or withdrawals due to AEs (p = 0.17). Overall incidence of nonserious AEs possibly related to treatment was higher with DFP than DFO (59% vs. 33%; p = 0.01). Transient elevation of liver enzymes was significantly higher with DFP (p = 0.03). 1 child developed agranulocytosis during parvovirus infection, which resolved the following day. In the efficacy population, there was no significant difference in mean (SD) LIC decrease from baseline to 12 months with DFP compared to DFO (-3.39 ± 4.24 mg/g vs. -2.99 ± 3.16 mg/g, respectively; p = 0.57). This pediatric subgroup analysis corroborates previous findings that DFP is comparable to DFO in safely reducing LIC in children with transfusion-dependent anemias. No new safety concerns were observed in children that have not been previously noted in other populations. The present findings on DFP may benefit children with SCD and their healthcare providers when considering effective iron chelation therapy that may also address treatment-adherence concerns.