Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study.
OBJECTIVE
This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or beta-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC).


RESULTS
In patients with baseline LIC > or = 7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 +/- 0.14 mg/kg/d; greatest in DBA: 0.4 +/- 0.11 mg/kg/d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.


CONCLUSIONS
Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups.
Porter
John
J
University College London, London, UK. j.porter@ucl.ac.uk
Galanello
Renzo
R
Saglio
Giuseppe
G
Neufeld
Ellis J
EJ
Vichinsky
Elliott
E
Cappellini
Maria Domenica
MD
Olivieri
Nancy
N
Piga
Antonio
A
Cunningham
Melody J
MJ
Soulières
Denis
D
Gattermann
Norbert
N
Tchernia
Gilbert
G
Maertens
Johan
J
Giardina
Patricia
P
Kwiatkowski
Janet
J
Quarta
Giovanni
G
Jeng
Michael
M
Forni
Gian Luca
GL
Stadler
Michael
M
Cario
Holger
H
Debusscher
Louisette
L
Della Porta
Matteo
M
Cazzola
Mario
M
Greenberg
Peter
P
Alimena
Giuliana
G
Rabault
Bertrand
B
Gathmann
Insa
I
Ford
John Malcolm
JM
Alberti
Daniele
D
Rose
Christian
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D029503:Anemia, Diamond-Blackfan / Q000188:drug therapy*; D001565:Benzoates / Q000627:therapeutic use*; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011446:Prospective Studies; D013789:Thalassemia / Q000188:drug therapy*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000188:drug therapy*
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox