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 Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC Methods THALASSA was a randomized, double-blind, placebo-controlled study of two deferasirox regimens (5 and 10mg/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 6months before reaching LIC<3 (Period 1), and the 6months immediately before achieving LIC<3 (Period 2). Results Mean +/- SD deferasirox treatment duration up to reaching LIC<3 was 476 +/- 207d, and deferasirox dose was 9.7 +/- 3.0mg/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 LICLIC 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.