Saldanha E F, Ribeiro M F, Hirsch I, Spreafico A, Saibil S D, Butler M O
Department of Medicine, University of Toronto, Toronto, Canada; Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Department of Medicine, University of Toronto, Toronto, Canada; Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
ESMO Open. 2025 Apr;10(4):104496. doi: 10.1016/j.esmoop.2025.104496. Epub 2025 Mar 19.
Uveal melanoma is the most prevalent and aggressive intraocular malignancy affecting adults. Compared with cutaneous melanoma, uveal melanoma has distinct pathogenesis and molecular characteristics. Not surprisingly, it derives limited benefits from checkpoint inhibitors. Until recently, no systemic therapy had impacted survival outcomes for this patient population. Tebentafusp, a T-cell receptor-based molecule, is the first US Food and Drug Administration/European Medicines Agency-approved systemic therapy to improve the survival outcomes for uveal melanoma patients expressing HLA-A∗02:01. Only 45%-50% of this patient population will express the HLA-A∗02:01, however, and therefore are eligible to receive this novel treatment. Moreover, global access to tebentafusp is limited, and there are no guidelines to aid clinicians in decision-making regarding treatment. In this review, we outline our experience as Canada's largest tertiary referral centre in managing metastatic uveal melanoma patients and provide a comprehensive overview of the currently available treatment options, challenging scenarios, and ongoing clinical trials for patients with metastatic uveal melanoma.
葡萄膜黑色素瘤是影响成年人的最常见且侵袭性最强的眼内恶性肿瘤。与皮肤黑色素瘤相比，葡萄膜黑色素瘤具有独特的发病机制和分子特征。毫不奇怪，它从检查点抑制剂中获得的益处有限。直到最近，还没有全身治疗方法能影响该患者群体的生存结局。替贝福司是一种基于T细胞受体的分子，是首个获得美国食品药品监督管理局/欧洲药品管理局批准的、可改善表达HLA-A∗02:01的葡萄膜黑色素瘤患者生存结局的全身治疗药物。然而，该患者群体中只有45%-50%会表达HLA-A∗02:01，因此有资格接受这种新疗法。此外，替贝福司在全球的可及性有限，并且没有指导临床医生进行治疗决策的指南。在这篇综述中，我们概述了作为加拿大最大的三级转诊中心在管理转移性葡萄膜黑色素瘤患者方面的经验，并全面介绍了转移性葡萄膜黑色素瘤患者目前可用的治疗选择、具有挑战性的情况以及正在进行的临床试验。
