Duek Adrian, Tzinman Alexandra, Maziuk Kira, Levy Assaf, Ellis Martin, Stemer Galia, Shacham Abulafia Adi, Cohen Amos, Lavi Noa, Ronson Aaron, Braester Andrey, Shapira Shirley, Canaani Jonathan, Volchek Yulia, Leiba Ronit, Leiba Merab
Samson Assuta Ashdod Public Hospital, Ashdod, Israel.
Ben-Gurion University of the Negev, Beersheba, Israel.
Acta Haematol. 2024 Sep 12:1-7. doi: 10.1159/000540906.
In recent years, fedratinib, a selective JAK2 inhibitor, has emerged as a potential therapeutic option for patients who have failed or are intolerant to ruxolitinib. Despite the promising results observed in clinical studies, real-world evidence from the USA and Europe suggests that the efficacy of fedratinib may be less conclusive. We report the characteristics, treatment patterns, and clinical outcomes of patients with myelofibrosis (MF) treated with fedratinib following ruxolitinib failure in Israel's clinical practice.
This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment.
We extracted data for 16 eligible patients. Approximately 62.5% of the patients were female, and the median age was 77 (range: 63-85) years. The median duration of ruxolitinib therapy was 17 months (range: 3-84) months. Before the initiation of fedratinib, the median spleen size by palpation was 15.5 cm below the costal margin (range: 4-22 cm). After 3 months the median spleen size was 13 cm below the costal margin (range: 2-21 cm). Only 2 patients showed minimal improvement after 6 months, while 3 patients progressed, and 2 patients showed no change in the spleen size. The spleen response did not improve after 12 months of treatment. At this point, the median spleen size was 19 cm below the costal margin (range: 2-30 cm). Regarding the MF-related symptoms, 43.75% (n = 7) of patients reported some improvement, 37.5% (n = 6) showed no changes, whereas 18.75% (n = 3) of the population complained of worsening. Gastrointestinal toxicity was the most frequent adverse effect of the drug, while 31% of patients died.
Our observations showed that in MF patients who have failed to ruxolitinib, the therapeutic value from fedratinib may be modest, especially when exposure time to ruxolitinib was more than 12 months. Early switching from ruxolitinib to fedratinib may yield a better result.
近年来，选择性JAK2抑制剂费拉替尼已成为对鲁索替尼治疗失败或不耐受患者的一种潜在治疗选择。尽管在临床研究中观察到了有前景的结果，但来自美国和欧洲的真实世界证据表明，费拉替尼的疗效可能不太明确。我们报告了以色列临床实践中鲁索替尼治疗失败后接受费拉替尼治疗的骨髓纤维化（MF）患者的特征、治疗模式和临床结局。
这项回顾性患者病历审查纳入了经医生报告诊断为MF的成年人，他们在停用鲁索替尼后开始使用费拉替尼。描述性分析描述了从MF诊断到鲁索替尼和费拉替尼治疗期间的患者特征、临床结局和治疗模式。
我们提取了16例符合条件患者的数据。约62.5%的患者为女性，中位年龄为7岁（范围：63 - 85岁）。鲁索替尼治疗的中位持续时间为17个月（范围：3 - 84个月）。在开始费拉替尼治疗前，触诊脾脏大小的中位值为肋缘下15.5厘米（范围：4 - 22厘米）。3个月后，脾脏大小的中位值为肋缘下厘米（范围：2 - 21厘米）。6个月后只有2例患者有轻微改善，3例患者病情进展，2例患者脾脏大小无变化。治疗12个月后脾脏反应未改善。此时，脾脏大小的中位值为肋缘下19厘米（范围：2 - 30厘米）。关于MF相关症状，43.75%（n = 7）的患者报告有一些改善，37.5%（n = 6）无变化，而18.75%（n = 3）的患者抱怨症状恶化。胃肠道毒性是该药物最常见的不良反应，31%的患者死亡。
我们的观察结果表明，在鲁索替尼治疗失败的MF患者中，费拉替尼的治疗价值可能有限，尤其是当鲁索替尼的暴露时间超过12个月时。早期从鲁索替尼换用费拉替尼可能会产生更好的结果。
