S115: LONG-TERM EFFICACY AND SAFETY OF DEFERIPRONE FOR PATIENTS WITH SICKLE CELL DISEASE OR OTHER ANEMIAS

Abstract

Background: FIRST-EXT was a prospective, multicenter, single-arm, open-label extension of the FIRST study in patients with sickle cell disease (SCD) and other transfusion-dependent anemias. In FIRST, patients were randomly assigned 2:1 to receive oral deferiprone (DFP) or parenteral deferoxamine (DFO) for 12 months. The noninferiority of DFP versus DFO was previously reported.1 Here we report the efficacy and safety of DFP in FIRST-EXT. Aims: To evaluate the long-term efficacy and safety of DFP in iron-overloaded patients with SCD or other anemias. Methods: Patients who completed FIRST could enter FIRST-EXT for up to 2 years. Patients previously treated with DFP continued on DFP (DFP-DFP), while those previously treated with DFO were switched to DFP (DFO-DFP). Baseline was defined as the start of FIRST for DFP-DFP patients, and the start of FIRST-EXT for DFO-DFP patients. Efficacy endpoints were yearly changes from baseline in liver iron concentration (LIC), cardiac MRI T2*, and serum ferritin (SF). We also report adverse drug reactions (ADRs), defined as adverse events at least possibly related to DFP. All patients provided informed consent or assent. Results: Patients (N=134: 89 DFP-DFP; 45 DFP-DFO) were 60.4% male, with a mean (SD) age of 16.2 (8.6) years. Most (85.8%) had SCD; 14.2% had other anemias. At baseline, all patients had elevated (≥1.8 mg/g dry weight [dw]) LIC; all but one had elevated (females >300 µg/L, males >400 µg/L) SF; and all had cardiac MRI T2* in the normal range (≥20 ms). A significant, progressive decline was seen in LIC, with mean (SD) changes from baseline to years 1, 2, and 3 of -2.64 (4.64), -3.91 (6.38), and -6.64 (7.72) mg/g dw, respectively (P<0.01 for all). A decline was also seen in SF, with mean (SD) changes from baseline to years 1, 2, and 3 of -1 (1986), -771 (2171), and -1016 (3617) µg/L, respectively (P<0.05 for years 2 and 3). Cardiac MRI T2* values changed little from baseline. The most frequent ADRs were neutropenia (9.0%), decreased neutrophil count (9.0%), and abdominal pain (7.5%); 2 patients (1.5%) experienced agranulocytosis. One patient withdrew due to ADRs of thrombocytopenia and neutropenia, which resolved. Another patient withdrew due to generalized edema and died for reasons unknown 17 days after withdrawal from the study. Conclusions: DFP long-term use (≤3 years) was effective in controlling body iron load in patients with SCD and other anemias. There were no new safety concerns.