地拉罗司对伴有铁过载的再生障碍性贫血患者的祛铁疗效及安全性——一项单臂、多中心、前瞻性临床研究

OBJECTIVE: To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload. METHODS: A single arm, multi-center, prospective, open-label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(−1)·d(−1), and the safety in 64 AA patients with iron overload. RESULTS: All patients started their deferasirox treatment with a daily dose of 20 mg·kg(−1)·d(−1). The mean actual dose was (18.6±3.60) mg · kg(−1)·d(−1). The median SF decreased from 4 924 (2 718–6 765)µg/L at baseline (n=64) to 3 036 (1 474–5 551)µg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126–2 125)µg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580–4 806)µg/L [5 271(3 420–8 278)µg/L at baseline; 3 036(1 474–5 551)µg/L after 12 months' treatment; the percentage change from baseline as 42%] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%) and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%) patients had two consecutive values >ULN, 10(26.3%) patients had two consecutive values >1.33 baseline values, but only 1(2.6%) patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post-baseline values >5×ULN or >10×ULN during the whole study. In AA patients with low baseline PLT count (less than 50×10(9)/L), there was no decrease for median PLT level during 12 months' treatment period. CONCLUSION: AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.