PF504 LONG‐TERM SEQUENTIAL DEFERIPRONE AND DEFERASIROX THERAPY IN TRANSFUSION‐DEPENDENT THALASSEMIA PATIENTS: A PROSPECTIVE CLINICAL TRIAL
Authors: A. Vitrano, G.B. Ruffo, D.G. D’Ascola, V. Caruso, A. Filosa, N. Masera, L. Pitrolo, P. Rigano, L. Cuccia, R. Di Maggio, A. Maggio
Journal: HemaSphere (2019)

Background: Iron overload is the main risk factor for morbidity and mortality in patients (pts) with transfusion dependent thalassemia (TDT). Therefore, life‐long iron chelation therapy is necessary for prevention of morbidities and long‐term survival. Three different chelating agents are currently available to treat iron burden in TDT pts: Deferoxamine (DFO) which is given subcutaneously, and 2 oral agents, Deferasirox (DFX) and Deferiprone (DFP). The possibility of using both oral chelators in a sequential manner remains of interest based on evidence that DFX and DFP have the liver and heart as their main target organ, respectively. Since the sequential administration of both oral chelators in monotherapy could be associated with a lower rate of adverse events (AEs), a prospective clinical trial to study this hypothesis was conducted. Aims: The aim was to assess the safety and effectiveness of the sequential DFP and DFX treatment in TDT pts, as measured by changes in SF, liver and cardiac MRI‐T2 ∗ , over time. Methods: This was a multicenter prospective clinical trial to assess effectiveness and safety of sequential DFP and DFX treatment in TDT pts. Data were collected at the coordinating centre (A.O.V. Cervello, U.O.C. di Ematologia II, Palermo, Italy). A total of 21 consecutive patients were followed at 6 Italian centres between 2010 and 2014. Trial interventions included sequential treatment with oral DFX dispersible tablet at the dose of 30 mg/kg/day for 3 days a week and oral DFP at a dose of 75 mg/kg/day every 6–8 hours for the remaining 4 consecutive days. The planned duration of the study was 5 years. However, since sample size was not reached, it was interrupted on April 10, 2014. Data consisted of repeated measurement on the same patient over time. Linear mixed‐effects (LME) models for repeated measurements were used to assess the effect of the sequential DFX and DFP therapy on SF levels, septum cardiac MRI‐T2 ∗ , and liver MRI‐T2 ∗ over time. Results: Overall, 21 TDT pts (8 [38.1%] males and 13 [61.9%] females) were enrolled in this trial. Patients’ median age was 32 years (range: 16 to 50). Mean total blood transfusion was 159.2 ± 35.3 ml/kg/year with a mean iron intake of 9.6 ± 0.6 mg/year. The median follow‐up was 32.2 months (range: 1 to 57). Results from the fitted LME model suggested a non‐statistically significant linear increase over time of the mean SF level (Coeff. 0.33 [SE 5.77], 95% CI −10.9 to 11.6, p ‐value = 0.954), as shown in Figure 1. The mean values of septum cardiac MRI‐T2 ∗ was 31.3 ms and 37.3 ms at baseline and at the end of follow‐up, respectively. The estimated results of the LME model for the mean liver T2 ∗ suggested that there is a statistically signficant linear increase over time (Coeff. 0.13 [SE 0.04], 95% CI 0.05 to 0.21, p ‐value = 0.001). Similarly, for the mean septum cardiac MRI‐T2 ∗ , results suggested that there is a statistically signficant linear increase over time (Coeff. 0.22 [SE 0.06], 95% CI 0.09 to 0.33, p ‐value&lt; 0.001). None of the patients developed iron overload in the liver or heart during sequential DFX and DFP iron chelation treatment. No moderate/severe adverse events were observed over 36 months. Summary/Conclusion: In our trial, sequential regimen of DFP and DFX maintained SF levels and removed iron from the heart and liver as evident from improvement in MRI‐T2 ∗ values. None of the pts experienced moderate or severe adverse events. Our data suggest the need to design new and wider studies to check this daily sequential therapy as an effective treatment option in those TDT pts who do not tolerate either mono or combined therapy. image