Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30 mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10 mg/kg/day. Mean actual dose ± SD over 1 year was 14.70 ± 5.48 mg/kg/day. At week 52, mean LIC ± SD decreased significantly from 15.13 ± 10.72 mg Fe/g dw at baseline to 8.46 ± 6.25 mg Fe/g dw (absolute change from baseline, -6.68 ± 7.02 mg Fe/g dw [95% CI: -7.91, -5.45]; P < 0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n = 6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients.
A.T., T., M.D., C., Y., A., J.B., P., Z., K., V., V., … Y.-R., L. (2016). Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study. Blood Cells, Molecules, and Diseases, 57, 23–29. https://doi.org/10.1016/j.bcmd.2015.11.002