Background Iron chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies. Objective To evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with low- or intermediate-1-risk MDS. Design Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602). Setting 60 centers in 16 countries. Participants 225 patients with serum ferritin levels greater than 2247 pmol/L; prior receipt of 15 to 75 packed red blood cell units; and no severe cardiac, liver, or renal abnormalities. Intervention Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76). Measurements The primary end point was EFS, defined as time from date of randomization to first documented nonfatal event (related to cardiac or liver dysfunction and transformation to acute myeloid leukemia) or death, whichever occurred first. Results Median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% CI, 3.2 to 4.3 years] vs. 3.0 years [CI, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [CI, 0.42 to 0.96]). Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (≥15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration. Limitations The protocol was amended from a phase 3 to a phase 2 study, with a reduced target sample size from 630 to 210 participants. There was differential follow-up between treatment groups. Conclusion The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients. Primary Funding Source Novartis Pharma AG.

中文翻译：

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低至中度1风险骨髓增生异常综合征输血依赖患者的铁螯合：一项随机试验。

背景尚未在随机研究中评估低危骨髓增生异常综合症（MDS）患者的铁螯合疗法（ICT）。目的评估低风险或中度1风险MDS的铁超负荷患者的无事件生存（EFS）和ICT的安全性。设计多中心，随机，双盲，安慰剂对照试验（TELESTO）。（ClinicalTrials.gov：NCT00940602）。在16个国家/地区设立60个中心。参与者225例血清铁蛋白水平高于2247 pmol / L；事先收到15至75个包装的红细胞单元；并且没有严重的心脏，肝脏或肾脏异常。干预性Deferasirox分散片（每天10至40 mg / kg）（n = 149）或匹配的安慰剂（n = 76）。测量主要终点是EFS，定义为从随机发生日期到首次记录的非致命事件（与心脏或肝脏功能障碍以及向急性髓细胞性白血病的转化有关）或死亡之间的时间，以先到者为准。结果Deferasirox组的中位治疗时间为1.6年（四分位间距[IQR]，0.5至3.1年），安慰剂组为1.0年（IQR，0.6至2.0年）。地拉罗司与安慰剂相比，中位EFS延长约1年（分别为3.9年[95％CI，3.2至4.3年]与3.0年[CI，2.2至3.7年]；危险比，0.64 [CI，0.42至0.96] ]）。不良事件发生在97.3％的地拉罗司接受者和90.8％的安慰剂接受者中。地拉罗司与安慰剂接受者的不良事件（经调整后的不良事件发生率（每100个患者治疗年≥15个事件））分别为24.7和23。腹泻为9，发热性为21.8对18.7，上呼吸道感染为16.7对22.7，血清肌酐浓度升高为15.9对0.9。局限性该方案从第3阶段修订为第2阶段，目标样本量从630人减少到210人。治疗组之间随访不同。结论：这些发现支持低危至中度1风险MDS的铁超负荷患者的ICT，与安慰剂相比EFS更长，且临床安全性可控。因此，可以在这些患者中考虑使用ICT。主要资金来源诺华制药股份公司。局限性该方案从第3阶段修订为第2阶段，目标样本量从630人减少到210人。治疗组之间随访不同。结论：这些发现支持低危至中度1风险MDS的铁超负荷患者的ICT，与安慰剂相比EFS更长，且临床安全性可控。因此，可以在这些患者中考虑使用ICT。主要资金来源诺华制药股份公司。局限性该方案从第3阶段修订为第2阶段，目标样本量从630人减少到210人。治疗组之间随访不同。结论：这些发现支持低危至中度1风险MDS的铁超负荷患者的ICT，与安慰剂相比EFS更长，且临床安全性可控。因此，可以在这些患者中考虑使用ICT。主要资金来源诺华制药股份公司。