Fedratinib is a predominantly JAK2 inhibitor that has shown efficacy in untreated and ruxolitinib-exposed patients with myelofibrosis (MF). Based on randomized clinical trial data, it is approved for use in patients with International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high-risk disease and is distinguished from ruxolitinib in that it can be administered without dose reduction in patients with thrombocytopenia, to a platelet count above 50,000/µL. In these trials, fedratinib achieved significant spleen volume reduction in ~30–45% of patients and improvement in total symptom scores in 35–40% with good tolerability. In contrast, recently published real-world data suggest that these responses may not be as robust outside clinical trials. In the context of routine clinical practice spleen responses are documented in only 13–68%, with varying degrees of symptom improvement. This may be due to the lack of a uniform definition of ruxolitinib failure, which may influence the timing of initiating fedratinib as a second-line treatment and result in a more prolonged exposure to ruxolitinib prior to intitaing fedratinib treatment. We suggest that given the growing number of drugs available for use in MF, recognizing the failure of first-line (and potentially subsequent) treatments is critical to allow timely transition to potentially more active agents, as highlighted by the data pertaining to fedratinib.
Fedratinib主要是一种JAK2抑制剂，在未经治疗及曾接受鲁索替尼治疗的骨髓纤维化（MF）患者中显示出疗效。基于随机临床试验数据，该药获批用于国际预后评分系统（IPSS）或动态国际预后评分系统（DIPSS）中危-2或高危患者，其与鲁索替尼的区别在于对血小板计数高于50,000/µL的血小板减少症患者无需减量给药。在这些试验中，约30–45%的患者实现显著脾体积缩小，35–40%的患者总症状评分改善，且耐受性良好。然而，近期发表的真实世界数据显示，在临床试验之外这些疗效可能不够显著。在常规临床实践中，仅13–68%的患者记录到脾脏应答，症状改善程度不一。这可能由于鲁索替尼治疗失败缺乏统一定义，影响了启用Fedratinib作为二线治疗的时机，导致开始Fedratinib治疗前鲁索替尼暴露时间延长。我们认为，随着MF可用药物日益增多，识别一线（及后续）治疗失败对及时转换至可能更有效的药物至关重要，Fedratinib的相关数据正凸显了这一点。
肿瘤(癌症)患者之家