Tartaglione Immacolata, Origa Raffaella, Kattamis Antonis, Pfeilstöcker Michael, Gunes Sibel, Crowe Susanne, Fagan Niamh, Vincenzi Beatrice, Ruffo Giovan Battista
Department of Woman, Child and of General and Specialist Surgery, University of Campania Luigi Vanvitelli, Naples, Italy.
Ospedale Pediatrico Microcitemico "A.Cao," A.O. "G.Brotzu", Cagliari, Italy.
Exp Hematol Oncol. 2020 Aug 10;9:20. doi: 10.1186/s40164-020-00174-2. eCollection 2020.
Despite the proven benefits of iron chelation therapy (ICT) in the management of chronic iron overload and related complications, compliance to long-term ICT is challenging. Results from the ECLIPSE study, an open-label, randomized, multicenter, 2-arm, phase 2 study evaluated the safety of deferasirox dispersible tablet and film-coated tablet (FCT) formulations in patients with transfusion-dependent thalassemia (TDT) or very low, low, or intermediate risk myelodysplastic syndrome (MDS) treated over 24 weeks.
The aim of the current study (a 2-year, open-label, multicenter, single-arm, phase 3 study) is to evaluate the long-term safety and efficacy of deferasirox FCT in a subset of patients with TDT or lower/intermediate-risk MDS treated for 2 years after the completion of 24 weeks of treatment with deferasirox in the ECLIPSE phase 2 study.
Of 53 patients enrolled, 34 (64.2%) completed treatment and study. Adverse events (AEs) reported in most patients (~ 70%) were of mild to moderate severity. Headache and diarrhea were the most frequently (> 25%) reported AEs. None of the serious AEs (including 1 death) were considered treatment related. No new safety signal was identified, and long-term safety of deferasirox FCT was consistent with the known safety profile of deferasirox. No major concerns associated with gastrointestinal tolerability, renal safety, or hematological abnormalities (thrombocytopenia/neutropenia) were reported during the 2 years. Patients receiving deferasirox FCT had a treatment compliance (by pill count) of ~ 90% and persistence (continuous use for ≥ 30 days) of > 95%. Reduction in serum ferritin level was almost consistent starting from week 2 across all post-baseline time points (relative reduction: month 6, 19%; month 12, 29%).
The results from this 2-year interventional study suggest that the recommended dosing of deferasirox FCT, with better tolerability, palatability, and compliance, offers a favorable option of ICT for long-term management of iron overload and associated complications in TDT. ClinicalTrials.gov, NCT02720536. Registered 28 March 2016, https://www.clinicaltrials.gov/ct2/show/NCT02720536.
尽管铁螯合疗法（ICT）在治疗慢性铁过载及相关并发症方面已证实具有益处，但长期坚持ICT治疗仍具有挑战性。ECLIPSE研究是一项开放标签、随机、多中心、双臂2期研究，评估了去铁斯若分散片和薄膜包衣片（FCT）制剂在接受输血依赖型地中海贫血（TDT）或极低、低或中度风险骨髓增生异常综合征（MDS）患者中治疗24周的安全性。
本研究（一项为期2年的开放标签、多中心、单臂3期研究）的目的是评估在ECLIPSE 2期研究中接受去铁斯若治疗满24周后，对TDT或低/中度风险MDS患者亚组进行2年治疗的去铁斯若FCT的长期安全性和有效性。
在入组的53例患者中，34例（64.2%）完成了治疗和研究。大多数患者（约70%）报告的不良事件（AE）为轻度至中度严重程度。头痛和腹泻是报告频率最高（>25%）的AE。所有严重AE（包括1例死亡）均不被认为与治疗相关。未发现新的安全信号，去铁斯若FCT的长期安全性与已知的去铁斯若安全性特征一致。在2年期间，未报告与胃肠道耐受性、肾脏安全性或血液学异常（血小板减少症/中性粒细胞减少症）相关的重大问题。接受去铁斯若FCT治疗的患者的治疗依从性（通过药片计数）约为90%，持续用药率（连续使用≥30天）>95%。从第2周开始，所有基线后时间点血清铁蛋白水平的降低几乎一致（相对降低：第6个月，19%；第12个月，29%）。
这项为期2年的干预性研究结果表明，推荐剂量的去铁斯若FCT具有更好的耐受性、适口性和依从性，为长期管理TDT中铁过载及相关并发症提供了一种有利的ICT选择。ClinicalTrials.gov，NCT02720536。于2016年3月28日注册，https://www.clinicaltrials.gov/ct2/show/NCT02720536 。
