5. Therapy S141

elevated serum transaminase levels indicate progressiveliver damage. This analysis aims to assess the relationshipbetween reduction of SF, as an indicator of IO, and liverfunction assessed by alanine aminotransferase (ALT) levelsduring deferasirox treatment in MDS patients.Methods: Analysis is based on data from the 1-yearmulticentre EPIC trial. Transfusion-dependent MDS pa-tients initially received deferasirox 10−30mg/kg/day;5−10mg/kg/day dose adjustments (range 0−40mg/kg/day)were made every 3 months based on SF trends and safetymarkers. SF and ALT were assessed monthly by standardblood chemistry examinations.Results: 341 MDS patients were enrolled in the EPICtrial. Mean actual deferasirox dose during treatment was19.2±5.4mg/kg/day. Median SF at baseline, 3, 6, 9 and12 months was 2730, 2358, 2210, 2076 and 1904 ng/mL,respectively; median change from baseline in SF wassignificant at 12 months (P = 0.0019). Mean ALT atthe same time points was 59.7, 48.4, 42.0, 40.5 and36.1U/L, respectively; mean change from baseline in ALTat 12 months was significant (P < 0.0001; n = 169). Changesin SF and ALT were dependent on the actual dose received.There was a significant correlation between absolute changein SF and ALT from baseline to month 12 (P < 0.0001;Figure), indicating that a decrease in SF of 500 ng/mL wasassociated with a decrease in ALT of 21.64U/L.

n = 317

r = 0.56

P < 0.0001

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an

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fro

m b

as

eli

ne

in

ALT

(U

/L)

-250

-200

-150

-100

-50

0

50

100

150

200

250

Change from baseline in SF (ng/mL)

-8000 -6000 -4000 -2000 0 2000 4000 6000 8000

Regression line

Figure: Correlation between changes in SF and ALT inMDS patients receiving deferasirox.

Conclusions: In these chronically transfused MDS patients,the significant decrease in SF, and therefore IO, withdeferasirox treatment was associated with a significantimprovement in transaminases, an important indicator ofhepatic function.

P141 Efficacy and safety of deferasirox (Exjade®)in chelation-naive and previously chelatedpatients with transfusion-dependentmyelodysplastic syndromes (MDS)

M. Schmid1 °, A. Guerci-Bresler2, M. Della Porta3,K. Taylor4, D. Habr5, G. Domokos6, B. Roubert6, C. Rose7,N. Gattermann8. 1University Hospital, Ulm, Germany;2CHU Brabois (Groupe Francophone des Myelodysplasies),Vandoeuvre Cedex, France; 3University of Pavia MedicalSchool, IRCCS Policlinico S. Matteo, Pavia, Italy; 4MaterHospital, Brisbane, Australia; 5Novartis Pharmaceuticals,East Hanover, NJ, USA; 6Novartis Pharma AG, Basel,Switzerland; 7Hopital Saint-Vincent de Paul (GroupeFrancophone des Myelodysplasies), Lille, France;8Heinrich-Heine-University, Dusseldorf, Germany

Background: Although chronically transfused MDS pa-tients are at risk of iron overload, many remain undiagnosedand/or unchelated. Iron-overloaded MDS patients enrolledin the 1-year EPIC trial, both chelation-naive and previouslychelated, were assessed to evaluate baseline iron burden anddeferasirox treatment.Methods: 91% of patients started on deferasirox20mg/kg/day, 1.8% and 6.7% on 10 and 30mg/kg/day,respectively; 5−10mg/kg/day adjustments were made every3 months. Efficacy was assessed by measuring serumferritin (SF) monthly. Safety assessments included adverseevent (AE) and laboratory parameter monitoring.

0

500

1000

1500

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Previously chelated All patients

Med

ian

seru

m f

err

itin

(n

g/m

L)

Baseline Month 3 Month 6 Month 9 Month 12

Mean actual dose

(mg/kg/day)

Mean iron intake

(mg/kg/day)

18.7 ± 4.7 (n=165)

0.44 ± 0.53 (n=153)

19.7 ± 6.0 (n=175)

0.41 ± 0.29 (n=166)

19.2 ± 5.4 (n=340)

0.42 ± 0.42 (n=319)

*35%

*22%*26%

0Chelation-naive

*Relative median change from baseline in SF

Figure: Median SF during deferasirox treatment, bychelation history.

Results: 341 MDS patients were enrolled into EPIC;165 (48%) were chelation-naive, 176 (52%) previouslychelated with deferoxamine and/or deferiprone. 222 (65.1%)patients were aged �65, 104 (30.5%) aged 50−<65,14 (4.1%) aged 16−<50 and 1 (0.3%) aged 6−12years. Baseline demographics, including median SF, werecomparable between the two groups (Figure). At 12 months,median SF significantly decreased from baseline in theoverall population (P = 0.002) and in chelation-naive

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patients (P = 0.004). The SF decrease was not significantlydifferent between chelation-naive and previously chelatedpatients (P = 0.107).166 patients (48.7%) discontinued (78 [47.3%] naive,88 [50.0%] previously chelated), most commonly due toAEs (n = 78, 23%; 44 for drug-related AEs). Most commondrug-related AEs were diarrhoea (33%), nausea (13%),vomiting (8%) and abdominal pain (8%). Most (95%) AEswere of mild-to-moderate severity. There was no differencein AE profile between the two groups.Conclusions: Similar to chelation-naive patients, baselineSF levels in the previously chelated patients were>2500 ng/mL indicating that iron burden was not ade-quately managed with previous regimens. Irrespective ofchelation history deferasirox was effective in decreasingSF over 1 year and had a safety profile consistent withpreviously reported data in MDS. These data highlight theneed to monitor iron load in MDS and initiate effectivechelation therapy to reduce body iron burden.