Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome

J Clin Oncol. 2012 Jun 10;30(17):2134-9. doi: 10.1200/JCO.2010.34.1222. Epub 2012 Apr 30.

Abstract

Purpose: This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low- or intermediate-1-risk myelodysplastic syndrome (MDS).

Patients and methods: Eligible patients had serum ferritin ≥ 1,000 μg/L and had received ≥ 20 units of RBCs with ongoing transfusion requirements. The starting dose of deferasirox was 20 mg/kg/d, with dose escalation up to 40 mg/kg/d permitted.

Results: A total of 176 patients were enrolled, and 173 patients received therapy. Median serum ferritin decreased 23% in the 53% of patients who completed 12 months of treatment (n = 91), 36.7% in patients who completed 2 years (n = 49), and 36.5% in patients who completed 3 years (n = 33) despite continued transfusion requirement. Reduction in serum ferritin significantly correlated with ALT improvement (P < .001). Labile plasma iron (LPI) was measured quarterly during the first year of the study. Sixty-eight patients (39.3%) had elevated LPI at baseline. By week 13, LPI levels normalized in all patients with abnormal baseline level. Fifty-one (28%) of 173 patients experienced hematologic improvement by International Working Group 2006 criteria; of these, only seven patients received growth factors or MDS therapy. Over the 3-year study, 138 (79.8%) of 173 patients discontinued therapy, 43 patients (24.8%) because of adverse events or disease progression and 23 patients (13.2%) because of abnormal laboratory values. The most common drug-related adverse events were gastrointestinal disturbances and increased serum creatinine. There were 28 deaths, none of which were considered related to deferasirox.

Conclusion: Deferasirox reduces serum ferritin and LPI in transfusion-dependent patients with MDS. A subset of patients had an improvement in hematologic and hepatic parameters.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Benzoates / pharmacology*
  • Deferasirox
  • Erythrocyte Transfusion / methods*
  • Female
  • Ferritins / blood*
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Iron / blood*
  • Iron Chelating Agents / pharmacology*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / blood*
  • Myelodysplastic Syndromes / drug therapy*
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • Triazoles / pharmacology*

Substances

  • Benzoates
  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Iron Chelating Agents
  • Membrane Proteins
  • Triazoles
  • Ferritins
  • Iron
  • Deferasirox