Deferasirox for transfusion‐dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial)
- 10 April 2014
- journal article
- clinical trial
- Published by Wiley in European Journal of Haematology
- Vol. 92 (6), 527-536
- https://doi.org/10.1111/ejh.12300
Abstract
Background: In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted. Methods: The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined. Results: Of 159 participants enrolled from 37 Italian centers, 152 received ≥1 dose of deferasirox (initiated at 10-20 mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966 ng/mL to 1475 ng/mL (P < 0.0001). The cumulative incidence of transfusion independence, adjusted for death and disease progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12 months, respectively. Conclusions: Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independenceKeywords
This publication has 44 references indexed in Scilit:
- Differential effects of the type of iron chelator on the absolute number of hematopoietic peripheral progenitors in patients with -thalassemia majorHaematologica, 2012
- Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromesHaematologica, 2012
- Deferasirox treatment of iron‐overloaded chelation‐naïve and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjangeEuropean Journal of Haematology, 2011
- Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndromeHaematologica, 2010
- Deferasirox is a powerful NF- B inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavengingHaematologica, 2010
- Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromesHaematologica, 2010
- Relative response of patients with myelodysplastic syndromes and other transfusion‐dependent anaemias to deferasirox (ICL670): a 1‐yr prospective studyEuropean Journal of Haematology, 2007
- A Proportional Hazards Model for the Subdistribution of a Competing RiskJournal of the American Statistical Association, 1999
- A new method of classifying prognostic comorbidity in longitudinal studies: Development and validationJournal of Chronic Diseases, 1987