Cardiac iron load and function in transfused patients treated with deferasirox (the MILE study)

Eur J Haematol. 2017 Feb;98(2):97-105. doi: 10.1111/ejh.12793. Epub 2016 Sep 20.

Abstract

Objectives: To assess the effect of iron chelation therapy with deferasirox on cardiac iron and function in patients with transfusion-dependent thalassemia major, sickle cell disease (SCD), and myelodysplastic syndromes (MDS).

Methods: This phase IV, single-arm, open-label study over 53 wk evaluated the change in cardiac and liver iron load with deferasirox (up to 40 mg/kg/d), measured by magnetic resonance imaging (MRI).

Results: Cardiac iron load (myocardial T2*) significantly improved (P = 0.002) overall (n = 46; n = 36 thalassemia major, n = 4 SCD, n = 6 MDS). Results were significant for patients with normal and moderate baseline cardiac iron (P = 0.017 and P = 0.015, respectively), but not in the five patients with severe cardiac iron load. Liver iron concentration (LIC) significantly decreased overall [mean LIC 10.4 to 8.2 mg Fe/g dry tissue (dw); P = 0.024], particularly in those with baseline LIC >7 mg Fe/g dw (19.9 to 15.6 mg Fe/g dw; P = 0.002). Furthermore, myocardial T2* significantly increased in patients with LIC <7 mg Fe/g dw, but not in those with a higher LIC. Safety was consistent with previous reports.

Conclusions: Once-daily deferasirox over 1 yr significantly increased myocardial T2* and reduced LIC. This confirms that single-agent deferasirox is effective in the management of cardiac iron, especially for patients with myocardial T2* >10 ms (Clinicaltrials.gov identifier: NCT00673608).

Keywords: cardiac iron; deferasirox; hepatic iron; magnetic resonance imaging iron assessment; transfusional siderosis.

Publication types

  • Clinical Trial, Phase IV

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzoates / pharmacology
  • Benzoates / therapeutic use*
  • Blood Transfusion*
  • Chelation Therapy*
  • Deferasirox
  • Female
  • Ferritins / blood
  • Heart Function Tests
  • Hemoglobinopathies / complications
  • Hemoglobinopathies / therapy
  • Humans
  • Iron / metabolism*
  • Iron Chelating Agents / pharmacology
  • Iron Chelating Agents / therapeutic use*
  • Iron Overload / diagnosis
  • Iron Overload / drug therapy*
  • Iron Overload / etiology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Transfusion Reaction
  • Treatment Outcome
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*
  • Young Adult

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Ferritins
  • Iron
  • Deferasirox

Associated data

  • ClinicalTrials.gov/NCT00673608