title: Efficacy and safety of deferasirox at low and high iron burdens: results from the EPIC magnetic resonance imaging substudy.
abstract: The effect of deferasirox dosing tailored for iron burden and iron loading based on liver iron concentration (LIC) was assessed over 1 year in less versus more heavily iron-overloaded patients in a substudy of the Evaluation of Patients' Iron Chelation with Exjade®. Deferasirox starting dose was 10-30 mg/kg/day, depending on blood transfusion frequency, with recommended dose adjustments every 3 months. Therapeutic goals were LIC maintenance or reduction in patients with baseline LIC <7 or ≥7 mg Fe/g dry weight (dw), respectively. Changes in LIC (R2-magnetic resonance imaging) and serum ferritin after 1 year were assessed. Adverse events (AEs) and laboratory parameters were monitored throughout. Of 374 patients, 71 and 303 had baseline LIC <7 and ≥7 mg Fe/g dw, respectively; mean deferasirox doses were 20.7 and 27.1 mg/kg/day (overall average time to dose increase, 24 weeks). At 1 year, mean LIC and median serum ferritin levels were maintained in the low-iron cohort (-0.02 ± 2.4 mg Fe/g dw, -57 ng/mL; P = not significant) and significantly decreased in the high-iron cohort (-6.1 ± 9.1 mg Fe/g dw, -830 ng/mL; P < 0.0001). Drug-related gastrointestinal AEs, mostly mild to moderate, were more frequently reported in the <7 versus ≥7 mg Fe/g dw cohort (39.4 versus 20.8 %; P = 0.001) and were not confounded by diagnosis, dosing, ethnicity, or hepatitis B and/or C history. Reported serum creatinine increases did not increase in low- versus high-iron cohort patients. Deferasirox doses of 20 mg/kg/day maintained LIC <7 mg Fe/g dw and doses of 30 mg/kg/day were required for net iron reduction in the high-iron cohort, with clinically manageable safety profiles. The higher incidence of gastrointestinal AEs at lower iron burdens requires further investigation.
authors.affiliation: UCL Cancer Institute, Department of Haematology, University College London, 72 Huntley Street, London, UK. j.porter@ucl.ac.uk
authors.forename: J B
authors.initials: JB
authors.lastname: Porter
authors.forename: M S
authors.initials: MS
authors.lastname: Elalfy
authors.forename: A T
authors.initials: AT
authors.lastname: Taher
authors.forename: Y
authors.initials: Y
authors.lastname: Aydinok
authors.forename: L L
authors.initials: LL
authors.lastname: Chan
authors.forename: S-H
authors.initials: SH
authors.lastname: Lee
authors.forename: P
authors.initials: P
authors.lastname: Sutcharitchan
authors.forename: D
authors.initials: D
authors.lastname: Habr
authors.forename: N
authors.initials: N
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: El-Beshlawy
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002769:Cholelithiasis / Q000139:chemically induced; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D003404:Creatinine / Q000097:blood; D000077588:Deferasirox; D004487:Edema / Q000139:chemically induced; D005006:Ethnicity; D005260:Female; D005293:Ferritins / Q000097:blood; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000150:complications / Q000473:pathology / Q000628:therapy; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D007501:Iron / Q000032:analysis*; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019190:Iron Overload / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D011446:Prospective Studies; D013789:Thalassemia / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D065227:Transfusion Reaction; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D003404:Creatinine; D007501:Iron; D000077588:Deferasirox