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

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.

• Authors: Alan F List, Maria R Baer, David P Steensma, Azra Raza, Jason Esposito, Noelia Martinez-Lopez, Carole Paley, John Feigert, Emmanuel Besa
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 17 Pg. 2134-9 (Jun 10 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22547607 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, drug therapy)
• Prospective Studies
• Time Factors
• Treatment Outcome
• Triazoles (pharmacology)