Approaching low liver iron burden in chelated patients with non-transfusion-dependent thalassemia: the safety profile of deferasirox.
OBJECTIVE
Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over-chelation emerges as patients reach low, near-normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3.


METHODS
THALASSA was a randomized, double-blind, placebo-controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1-yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end-of-core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2).


RESULTS
Mean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure-adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment.


CONCLUSIONS
The deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over-chelation.
American University of Beirut, Beirut, Lebanon.
Ali T
AT
Taher
John B
JB
Porter
Vip
V
Viprakasit
Antonis
A
Kattamis
Suporn
S
Chuncharunee
Pranee
P
Sutcharitchan
Noppadol
N
Siritanaratkul
Raffaella
R
Origa
Zeynep
Z
Karakas
Dany
D
Habr
Zewen
Z
Zhu
M Domenica
MD
Cappellini
D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use; D000077588:Deferasirox; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D013789:Thalassemia / Q000150:complications*; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000077588:Deferasirox
iron chelation; iron overload; thalassemia