Deferasirox effectively reduces iron overload in non-transfusion-dependent thalassemia (NTDT) patients: 1-year extension results from the THALASSA study

Abstract

Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload that requires chelation to levels below the threshold associated with complications. This can take several years in patients with high iron burden, highlighting the value of long-term chelation data. Here, we report the 1-year extension of the THALASSA trial assessing deferasirox in NTDT; patients continued with deferasirox or crossed from placebo to deferasirox. Of 133 patients entering extension, 130 completed. Liver iron concentration (LIC) continued to decrease with deferasirox over 2 years; mean change was -7.14 mg Fe/g dry weight (dw) (mean dose 9.8 ± 3.6 mg/kg/day). In patients originally randomized to placebo, whose LIC had increased by the end of the core study, LIC decreased in the extension with deferasirox with a mean change of -6.66 mg Fe/g dw (baseline to month 24; mean dose in extension 13.7 ± 4.6 mg/kg/day). Of 166 patients enrolled, 64 (38.6 %) and 24 (14.5 %) patients achieved LIC <5 and <3 mg Fe/g dw by the end of the study, respectively. Mean LIC reduction was greatest in patients with the highest pretreatment LIC. Deferasirox progressively decreases iron overload over 2 years in NTDT patients with both low and high LIC. Safety profile of deferasirox over 2 years was consistent with that in the core study.

Fig. 1

Starting doses in the THALASSA extension study. *Wait until LIC >5 mg Fe/g dw and then restart at 5 mg/kg/day if 5 mg/kg/day was effective before interruption or at 10 mg/kg/day if 10–20 mg/kg/day was effective before interruption

Fig. 2

Patient disposition (groups reported in manuscript shaded in gray)

Fig. 3

Absolute change ± SD in LIC with deferasirox treatment up to 2 years

Fig. 4

a Mean ± SD absolute change in LIC by extension baseline LIC categories from extension baseline to month 24. b Mean ± SD absolute change in LIC by average actual dose categories from extension baseline to month 24 (all patients n = 133)

Fig. 5

Median absolute change (±25th/75th percentiles) in serum ferritin over time with deferasirox treatment for up to 2 years

Fig. 6

Mean ALT, serum creatinine, creatinine clearance, and urinary protein/creatinine ratio over 2 years. Measurements in month 24 were defined as those with study day greater than 30 × 24 − 15 = 705. In all safety analyses, the observations or measurements after 28 days of the last treatment would be excluded