Deferasirox for transfusion-dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial)
Deferasirox for transfusion-dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial)
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DOI：
10.1111/ejh.12300
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发表时间：
2014-06-01
影响因子：
3.1
通讯作者：
Tura, Sante
中科院分区：
文献类型：
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作者：
Angelucci, Emanuele;Santini, Valeria;Tura, Sante
背景在缺乏随机对照试验数据支持铁螯合治疗输血依赖型骨髓增生异常综合征（MDS）患者的情况下，需要继续从大型前瞻性临床试验中获得证据，以评估铁螯合治疗在该患者人群中的疗效和安全性。方法采用前瞻性、开放性、单臂、多中心临床试验，对国际预后评分系统（International Prognostic Scoring System）低危或中危1型MDS患者及有输血相关铁超载证据的输血依赖患者进行地拉罗司的安全性和有效性评价。还检查了地拉罗司治疗对血液学应答和疾病进展的影响。结果在来自37个意大利中心的159名参与者中，152人接受了≥ 1剂地拉罗司（以10- 20 mg/kg/天开始，并酌情滴定），68人完成了研究。在84名停止地拉罗司治疗的患者中，22名在试验期间死亡，28名因不良事件（AE）退出。11例患者发生了14起治疗相关的3级AE，而未报告4级或5级药物相关AE。脱落的显著风险是基线时血清铁蛋白水平较高，MDS特异性合并症指数较高，诊断-入组间隔较短。中位血清铁蛋白水平从1966 ng/mL下降到1475 ng/mL（P
Background In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted. Methods The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined. Results Of 159 participants enrolled from 37 Italian centers, 152 received >= 1 dose of deferasirox (initiated at 10-20mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966ng/mL to 1475ng/mL (P