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. 2014 Oct 28;2014(10):CD007461.
doi: 10.1002/14651858.CD007461.pub3.

Deferasirox for managing iron overload in people with myelodysplastic syndrome

Joerg J Meerpohl  1 , Lisa K Schell, Gerta Rücker, Nigel Fleeman, Edith Motschall, Charlotte M Niemeyer, Dirk Bassler
Affiliations

Deferasirox for managing iron overload in people with myelodysplastic syndrome

Joerg J Meerpohl et al. Cochrane Database Syst Rev. .

Abstract

Background: The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of removing excess iron, iron chelation therapy, i.e. the pharmacological treatment of iron overload, is usually recommended. However, it is unclear whether or not the newer oral chelator deferasirox leads to relevant benefit.

Objectives: To evaluate the effectiveness and safety of oral deferasirox for managing iron overload in people with myelodysplastic syndrome (MDS).

Search methods: We searched the following databases up to 03 April 2014: MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File and four trial registries: Current Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), ICTRP (www.who.int./ictrp/en/), and German Clinical Trial Register (www.drks.de).

Selection criteria: Randomised controlled trials (RCTs) comparing deferasirox with no therapy, placebo or with another iron-chelating treatment schedule.

Data collection and analysis: We did not identify any trials eligible for inclusion in this review.

Main results: No trials met our inclusion criteria. However, we identified three ongoing and one completed trial (published as an abstract only and in insufficient detail to permit us to decide on inclusion) comparing deferasirox with deferoxamine, placebo or no treatment.

Authors' conclusions: We planned to report evidence from RCTs that evaluated the effectiveness of deferasirox compared to either placebo, no treatment or other chelating regimens, such as deferoxamine, in people with MDS. However, we did not identify any completed RCTs addressing this question.We found three ongoing and one completed RCT (published as an abstract only and in insufficient detail) comparing deferasirox with deferoxamine, placebo or no treatment and data will hopefully be available soon. These results will be important to inform physicians and patients on the advantages and disadvantages of this treatment option.

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Conflict of interest statement

Joerg Meerpohl enrolled two adolescents with thalassaemia and one with Diamond‐Blackfan anaemia in a post‐marketing surveillance study on deferasirox and participated once in a Novartis advisory board meeting on paediatric iron overload over five years ago. The other review authors have no known conflicts of interest.

Figures

1
1
Study flow diagram (update search performed in April 2014),
See this image and copyright information in PMC

Update of

References

References to studies excluded from this review

Angelucci 2012 {published data only}
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Gattermann 2009 {published data only}
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Ghoti 2009 {published data only}
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Greenberg 2006, US2 study {published data only}
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    1. Greenberg PL, Koller CA, Glynos T, Paley C, Schiffer C. Change in liver iron concentration (LIC), serum ferritin (SF) and labile plasma iron (LPI) over 1 year of deferasirox (Exjade ®) therapy in a cohort of patients with MDS. Leukemia Research 2009;33(Suppl 1):S120.
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Leitch 2007 {published data only}
    1. Leitch H, Ezzat H, Rollins MD, Goodman TA, Leger CS, Wong DHC, et al. Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy. Blood 2008;112(11):617. - PubMed
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Leitch 2009 {published data only}
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List 2006, US3 study {published data only}
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Messa 2008 {published data only}
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Metzgeroth 2009 {published data only}
    1. Metzgeroth G, Dinter D, Schultheis B, Dorn‐Beineke A, Lutz K, Leismann O, et al. Deferasirox in MDS patients with transfusion‐caused iron overload ‐ a phase‐II study. Annals of Hematology 2009;88(4):301‐10. - PubMed
Min 2008 {published data only}
    1. Cheong J‐W, Kim H‐J, Lee K‐H, Yoon S‐S, Lee JH, Park H‐S, et al. Efficacy of ICT with Deferasirox in transfusional iron overloaded patients with MDS or AA. Blood 2009;114(22):1466.
    1. Min Y, Cheong J, Kim H, Lee K, Yoon S, Lee J, et al. A multi‐center, open label study evaluating the efficacy of iron chelation therapy with deferasirox in transfusional iron overload patients with myelodysplastic syndromes or aplastic anemia using quantitative R2 MRI. Leukemia Research 2009;33(Suppl 1):S118‐9.
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Miyazawa 2006 {published data only}
    1. Iki S, Urabe A, Hata T, Ohyashiki K, Nakao S, Takatoku M, et al. Comparative pharmacokinetic/pharmacodynamic profiles in Japanese and Caucasian patients with transfusional hemosiderosis receiving treatment with deferasirox (Exjade®, ICL670). Blood 2006;108(11, Part 2):296B‐7B.
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Nolte 2013 {published data only}
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Peng 2013 {published data only}
    1. Peng P. Long LL, Huang ZK, Zhang L, Li XH, Feng X. Comparison of deferasirox and deferoxamine treatment in iron‐overloaded patients: liver iron concentration determined by quantitative MRI‐R2* [Chinese]. Chinese Journal of Radiology 2013;47(1):55‐9.
Pennell 2014, CORDELIA {published and unpublished data}
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Porter 2004 {published data only}
    1. Cazzola M, Gattermann N, Greenberg P, Maertens J, Soulières D, Rose M, et al. ICL670, a once‐daily oral iron chelator, is effective and well tolerated in patients with myelodysplastic syndrome (MDS) and iron overload. Haematologica 2005;90(Suppl 2):318.
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Rachmilewitz 2008 {published data only}
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Remacha 2010 {published data only}
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Rose 2007 {published data only}
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Wimazal 2009 {published data only}
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References to studies awaiting assessment

Castellano 2011 {published data only}
    1. Andrade‐Campos MM, Medrano‐Engay MB, Royo P, Giraldo P. Impact of chelation therapy on patients with iron overload. +12 months follow‐up after QUELAFER study. European Leukemia Net (ELN) Frontiers Meeting; 2013 Oct 11‐13; Prague. http://www.leukemia‐net.org/content/home/eln_meetings/eln_frontiers_meeting/e10287/infoboxCo.... Frankfurt: European LeukemiaNet, (accessed 03 April 2014).
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References to ongoing studies

NCT02038816 {unpublished data only}
    1. NCT02038816. Azacitidine plus deferasirox (ICL670) in higher risk myelodysplastic syndromes (MDS). http://clinicaltrials.gov/show/NCT02038816 (accessed 16 April 2014).
Novartis 2013 {unpublished data only}
    1. CICL670A2421. An open‐label, phase II, randomized, pilot study to assessthe effect in term of erythroid improvement of deferasiroxcombined with erythropoietin compared to erythropoietinalone in patients with low‐ and int‐1‐risk myelodysplasticsyndrome. https://www.clinicaltrialsregister.eu/ctr‐search/trial/2013‐000981‐12/ES.
    1. NCT01868477. Combination study of deferasirox and erythropoietin in patients with low‐ and Int‐1‐risk myelodysplastic syndrome. http://clinicaltrials.gov/show/NCT01868477 (accessed 16 April 2014).
TELESTO 2009 {unpublished data only}
    1. 2009‐012418‐38. A multi‐center, randomized, double‐blind, placebocontrolled clinical trial of deferasirox in patients with myelodysplastic syndromes (low/int‐1 risk) and transfusional iron overload. https://www.clinicaltrialsregister.eu/ctr‐search/search?query=eudract_nu....
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    1. NCT00940602. Myelodysplastic syndromes (MDS) event free survival with iron chelation therapy study (TELESTO). http://clinicaltrials.gov/show/NCT00940602 (accessed 16 April 2014).

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References to other published versions of this review

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