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Updated: May 21, 2025
Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
How we treat patients with metastatic uveal melanoma
E F Saldanha1, M F Ribeiro1, I Hirsch1
1Department of Medicine, University of Toronto, Toronto, Canada; Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Abstract:
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.
Insights
Tebentafusp is the first systemic therapy to improve survival for uveal melanoma patients with HLA-A∗02:01. However, limited eligibility and access necessitate exploring alternative treatments and clinical trials for this aggressive eye cancer.
Area of Science:
- Ophthalmology
- Oncology
- Immunology
Background:
- Uveal melanoma is an aggressive intraocular malignancy with distinct characteristics from cutaneous melanoma.
- Current systemic therapies, including checkpoint inhibitors, offer limited benefits for uveal melanoma.
- No systemic therapy had previously demonstrated improved survival outcomes for this patient population.
Purpose of the Study:
- To review current treatment options for metastatic uveal melanoma.
- To discuss challenging scenarios in managing uveal melanoma.
- To provide an overview of ongoing clinical trials for uveal melanoma.
Main Methods:
- Review of clinical experience at a large tertiary referral center.
- Comprehensive overview of available systemic therapies.
- Discussion of treatment challenges and future research directions.
Main Results:
- Tebentafusp is the first FDA/EMA-approved systemic therapy to improve survival in HLA-A∗02:01-positive uveal melanoma patients.
- Only 45-50% of uveal melanoma patients express HLA-A∗02:01, limiting tebentafusp eligibility.
- Global access to tebentafusp is restricted, and clinical guidelines are lacking.
Conclusions:
- Tebentafusp represents a significant advancement but has limitations in eligibility and access.
- Management of metastatic uveal melanoma requires consideration of alternative treatments and clinical trials.
- Further research and guideline development are crucial for optimal patient care.
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