Impact of Compliance, Ferritin and LIC on Long-Term Trends in Myocardial T2* with Deferasirox

Background : Previous reports on the effects of various iron chelation regimes, including deferasirox, have shown improvements in myocardial iron over a period of up to 1 year. However no longitudinal analysis of myocardial T2* (mT2*) trends with any chelator regimen beyond 1 year has been reported. Monitoring of mT2* has been part of standard management of transfusional iron overload at UCLH for over 8 years. In this study, we have analysed long-term trends in mT2* up to 4 years for patients entered into pre-registration and extension phases of deferasirox studies, 107 and 108, as well as factors that may determine such trends. Patients and Methods: 33 transfusion dependent patients with thalassaemia or rare anaemias, age range 7–51 years, had mT2*, and T2* LIC assessments repeated with a median interval of 14 months (3.6 occasions per patient) while receiving deferasirox. This allowed analysis of factors affecting trends in mT2* on a total of 104 observation periods (of a median of 371 days). Starting doses of 10–30mg/kg/day were predicated by baseline and 1 year biopsy LIC values according to study protocols. Subsequent dose adjustment depending on adverse events profile, trends of ferritin and serum creatinine, degree of proteinuria, or mT2* and T2* LIC was allowed at the investigators’ discretion. LIC was estimated from liver T2* with correction for liver R2. A maximum permissible chelator dose in the final two years of the study was 40mg/kg. Compliance was calculated from the % of intended doses that were missed over the period of observation, assessed from patient interviews conducted on monthly visits. 4 patients were excluded from analysis due to lack of an adequate baseline mT2* pre–treatment. At baseline, 13 patients had myocardial iron loading as evidenced by mT2* Results: Average baseline mT2* of 21.6ms improved significantly to 24.7ms (p= 0.046, n=29) at a median follow-up of 4 years (geometric mean 18.9ms and 20.7ms, respectively). The greatest improvement in mT2* was seen in the first year of treatment (0.16ms/month) and the least in the final year giving a median change over the 4 year period of 1.27ms/year. At 4 years, among patients with baseline T2* values 20ms all remained normal apart from one who received low dosing (10mg/kg) in the first months of the study. Analysis of factors associated with trends in mT2* revealed compliance, LIC, and ferritin as statistically significant. For each observation period, compliance nd , 3 rd , and 4 th year (p 12 mg/gdw was associated with worsening of mT2* (p=0.02). Conclusions: With long-term administration of deferasirox, we conclude that compliance should be maintained above 90% to optimize the sustained control of mT2*. Longitudinal control of LIC and ferritin may also be important to reducing the risk of myocardial iron loading in patients receiving long-term deferasiox treatment.