一例TEK突变静脉畸形中长期TIE2抑制：3年临床经验

摘要(中文译文)

静脉畸形（VMs）是一种慢血流血管异常，常由TIE2受体的体细胞激活突变驱动。药物治疗选择仍然有限；尽管使用西罗莫司抑制mTOR已显示出中等获益，但直接抑制TIE2具有强有力的生物学依据和新兴的临床证据。我们报告一例51岁患者，患有累及右侧颈部、胸部和上肢的弥漫性静脉畸形，伴有体细胞嵌合（L914F）变异。该疾病对常规治疗难治，并并发慢性凝血病。基于先前报道的一例患者，启动了选择性TIE2抑制剂rebastinib的同情用药治疗。在3年多的随访中，患者获得了持续的临床获益，表现为疼痛和炎症减轻、部分体积缩小、功能改善以及凝血病稳定，且毒性可控。不幸的是，药物生产的中断使得有必要尝试其他特异性较低的替代药物，如PI3K抑制剂alpelisib。这第二个长期临床经验支持TIE2抑制在特定突变型静脉畸形中的持续疗效和安全性，并凸显了因药物停用而产生的治疗缺口，强调了需要替代性靶向策略和前瞻性评估。

Abstract

Venous malformations (VMs) are slow-flow vascular anomalies frequently driven by somatic activating mutations in /TIE2 receptor. Medical treatment options remain limited; while mTOR inhibition with sirolimus has shown moderate benefit, direct TIE2 inhibition has a strong biological rationale and emerging clinical evidence. We report a 51-year-old patient with a diffuse VM involving the right cervical region, thorax, and upper extremity, associated with a somatic mosaic (L914F) variant. The disease was refractory to conventional therapies and complicated by chronic coagulopathy. Compassionate-use treatment with the selective TIE2 inhibitor rebastinib was initiated based on a previously reported patient. Over 3 years of follow-up, the patient experienced sustained clinical benefit with decreased pain and inflammation, partial volume reduction, functional improvement, and stabilization of coagulopathy with manageable toxicity. Unfortunately, the interruption in the production of the drug made it necessary to try other less specific alternatives like PI3K inhibitor alpelisib. This second long-term clinical experience supports the sustained efficacy and safety of TIE2 inhibition in selected -mutated VMs and highlights the therapeutic gap arised from drug discontinuation, underscoring the need for alternative targeted strategies and prospective evaluation.

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