美国克利夫兰诊所陶西格癌症中心Keith R. McCrae团队，研究了泊马度胺治疗遗传性出血性毛细血管扩张致鼻出血的疗效与安全性。这一研究成果于2024年9月19日发表在《新英格兰医学杂志》上。

遗传性出血性毛细血管扩张症（HHT）的特征是广泛的毛细血管扩张和动静脉畸形。主要临床表现是鼻出血，导致缺铁性贫血和健康相关生活质量降低。

研究组进行了一项随机、安慰剂对照试验，以评估泊马度胺治疗HHT的安全性和有效性。以2:1的比例随机分配患者，每天服用4mg泊马度胺或匹配的安慰剂，持续24周。主要结局是从基线到第24周鼻出血严重程度评分的变化（HHT中验证的出血评分；范围为0至10，评分越高，出血越严重）。减少0.71分或更多被认为具有临床意义。一个关键次要结局是HHT特异性生活质量评分（范围为0至16，评分越高表示限制越多）。

在计划的中期分析达到预先设定的疗效阈值后，该试验于2023年6月停止招募。共有144名患者接受了随机分组；95名患者被分配接受泊马度胺治疗，49名患者接受安慰剂治疗。基线平均（±SD）鼻出血严重程度评分为5.0±1.5，该值与中重度鼻出血一致。24周时，泊马度胺组和安慰剂组的鼻出血严重程度评分与基线相比的平均差异为-0.94分（95%置信区间[CI]，-1.57至-0.31；P=0.004）。两组之间HHT特异性生活质量评分变化的平均差异为-1.4分（95%CI，-2.6至-0.3）。与安慰剂组相比，泊马度胺组更常见的不良事件包括中性粒细胞减少症、便秘和皮疹。

研究结果表明，在HHT患者中，泊马度胺治疗导致鼻出血严重程度显著降低，具有临床相关性。没有发现意外的安全信号。

附：英文原文

Title: Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia

Author: Hanny Al-Samkari, Raj S. Kasthuri, Vivek N. Iyer, Allyson M. Pishko, Jake E. Decker, Clifford R. Weiss, Kevin J. Whitehead, Miles B. Conrad, Marc S. Zumberg, Jenny Y. Zhou, Joseph Parambil, Derek Marsh, Marianne Clancy, Lauren Bradley, Lisa Wisniewski, Benjamin A. Carper, Sonia M. Thomas, Keith R. McCrae

Issue&Volume: 2024-09-19

Abstract:

BACKGROUND

Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life.

METHODS

We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations).

RESULTS

The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was 0.94 points (95% confidence interval [CI], 1.57 to 0.31; P=0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was 1.4 points (95% CI, 2.6 to 0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash.

CONCLUSIONS

Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified.

DOI: NJ202409193911108

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2312749