Controversies in Iron Chelation in Myelodysplastic Syndromes

Aristoteles Giagounidis, MD, PhDDepartment of Haematology and Oncology

St. Johannes Hospital Duisburg, Germany

Heather A. Leitch, MD, PhD, FRCPCHematologist

Department of Medicine, Division of HematologySt. Paul’s Hospital

University of British ColumbiaVancouver, British Columbia, Canada

Iron Overload and Transfusion Dependency Independent Impact on Overall Survival and Leukaemic

Evolution in 902 Patients with MDS HR P Value

• Overall survival– Iron overload 52.4 <.0001– Transfusion dependency 8.8 <.0001

• Risk for evolution to AML– Iron overload 6.6 <.0001– Transfusion dependency 3.5 <.003

Sanz G, et al. 50th Annual ASH Meeting; December 6-9, 2008. Abstract 640.

Independent Predictors of Survival in MDS

Median Survival P valueTransfusion- Dependent 34 mos <.001 Independent 56 mosFerritin High (>1,000 ng/mL) 34 yrs <.001 <1,000 53 yrs

Arnan M, et al. 15th Congress of EHA, June 2010. Abstract 314.

Nonleukaemic Causes of Death in MDS and Relationship to Iron Overload

• Cardiac failure (CHF) 51%• Infection 31%• Haemorrhage 8%• Hepatic cirrhosis 8%• Unidentified 2%

Low-risk MDS: Cardiac failure is significantly more common in transfused than nontransfused patients (P=.01)

Malcovati L, et al. J Clin Oncol. 2005;23:7594-7603.

Iron Chelation and Overall Survival in Low/Int-1 MDS

• Median overall survival– No chelation therapy – 53 mos– Chelation therapy – 124 mos (p<.0003)

• Adequate chelation was the strongest factor associated with better overall survival in heavily transfused lower risk MDS patients

97 low or int-1 IPSS regularly transfused patients: 44 (45%) not chelated; 53 (55%) chelated for >6 mos

Rose C, et al. Leuk Res. 2010;34:864-870.

Hematologic Improvement in MDS Patients with Iron Chelation Therapy

Pts with Minor Erithroid Response*

After 6 mos 1/8After 9 mos 2/8After 12 mos 2/8

Total response rate 5/8 (60%)

8 MDS patients received ● Deferasirox 5-20 mg/kg/day, or ● Desferrioxamine 30 mg/kg/sc 3-4 times/week *Minor response = 50% reduction in RBC transfused

Molteni A, et al. 15th Congress of EHA, June 2010. Abstract 1410.

Patients most likely to benefit

from the treatment of iron

overload

Bennett JM, et al. Am J Hematol. 2008;83:858-861.

2008 Consensus Statement on Iron Overload in MDS

• Transfusion-dependent patients

• Ferritin levels >1000 ng/mL

• Low-risk MDS (IPSS low or Int-1; WHO RA and RARS and 5q-)

• Expected overall survival ≥1 year

• Candidates for allograft

• Need to preserve organ function

• Absence of comorbidities severely limiting prognosis

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