Poster Session II: Thalassemias
Thalassemia is the most common and severe chronic hemolytic anemia in Greece, the National Registry recently reporting more than 2000 transfusion-dependent patients. As a combined result of disease pathophysiology and transfusion treatment, thalassemic patients present with iron overload from an early age. Deferasirox (DFX), the newest of chelators used to excrete iron, was until recently administered in the form of dispersible tablets. However, the same active substance was licensed as film coated tablets (FCT) in an effort to overcome issues related to drug intolerance. Because of the same active substance being used, no clinical trials in iron overloaded patients were required from regulatory authorities.
Aim of the present study was to evaluate safety and efficacy of the new DFX formulation in pediatric patients with transfusion-dependent thalassemic syndromes.
Pediatric patients with transfusion-dependent thalassemia, followed at a single pediatric center, were enrolled. Patients were prospectively evaluated as to hepatic function, glomerular and tubular renal function, and liver and cardiac iron overload over a twelve-month period following initiation of DFX FCT. Drug related adverse events were recorded. Statistical analysis was performed by SPSS 23, Pearson Correlation and Wilcoxon test.
Out of 19 patients enrolled 12 (63%) were males. Mean patient age was 13.8 years (7-18 years). Prior to DFX FCT administration 14/19 patients (73%) were on the previous DFX formulation (dispersible tablet, DT) and 5/19 patients on a different iron chelator. At the end of study, mean ferritin values showed no statistically significant change. With regards to renal function, 18/19 patients (94.7%) presented with a reduction in glomerular filtration rate (GFR) at some time point during follow up, however, in no case was reduction found to be more than > 33% compared to baseline. Transient increase of spot urinary protein: creatinine ratio was reported in 4/19 patients (21%), and of spot urinary calcium: creatinine ratio in 18/19 patients (94.7%) - in no case increase reaching statistical significance. Mild, transient elevation of alanine transaminase (ALT) and of alkaline phosphatase was reported in 3/19 patients (15.7%) and of aspartate transaminase (AST) in 2 patients (10.5%). No statistically significant correlation was found between DFX FCT dose and laboratory parameters studied, i.e ferritin, GFR, protein: creatinine and calcium: creatinine ratio, AST, ALT or ALP. With regards to cardiac and liver magnetic resonance imaging (MRI), assessment at the beginning and end of study was performed in 8 out of 19 patients (42%). All patients presented with a reduction in liver iron, which reached the limit of statistical significance, and a statistically significant reduction in cardiac iron. Reported drug-related adverse events were mild gastrointestinal symptoms in 3/19 patients (15.8%) and skin rash in 1 patient (5.2%).
Study results demonstrated that the new DFX formulation is effective in reducing iron overload in thalassemic children, while maintaining a satisfactory safety profile. Improvements in formulation's mode of administration can increase treatment adherence and minimize iron toxicity. That, in combination with documented safety and efficacy, may improve quality of life for patients with transfusion-dependent thalassemia.