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Review
. 2023 Jun 8:19:100386.
doi: 10.1016/j.iotech.2023.100386. eCollection 2023 Sep.

Immuno-oncology approaches in uveal melanoma: tebentafusp and beyond

C Gerard  1   2 , B Shum  1   3 , P Nathan  4 , S Turajlic  1   3
Affiliations
Review

Immuno-oncology approaches in uveal melanoma: tebentafusp and beyond

C Gerard et al. Immunooncol Technol. .

Abstract

Uveal melanoma (UM) is the most common ocular malignancy in adults, associated with the poorest prognosis, with metastatic disease occurring in up to 50% of patients. In contrast to metastatic cutaneous melanoma, the use of immune checkpoint inhibitors is associated with poor outcomes in metastatic uveal melanoma (mUM). Tebentafusp, a bispecific molecule, has recently become the first treatment in decades to improve overall survival for mUM. This review summarises the existing and emerging immuno-oncology approaches for the treatment of mUM, and biomarkers of response and resistance to the same. Finally, we propose future research directions that could maximise treatment benefit to a wider pool of patients with UM.

Keywords: biomarkers; bispecific molecule; immunotherapy; metastatic uveal melanoma; tebentafusp.

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Figures

Figure 1
Figure 1
Classification of metastatic risk. TCGA, The Cancer Genome Atlas. Adapted from Smit et al., Robertson et al., Cell 2018, Royer-Bertrand et al., Jager et al., and Vichitvejpaisal et al.
Figure 2
Figure 2
Molecular targets in early-phase immuno-oncology trials in metastatic uveal melanoma (mUM). ctDNA, circulating tumour DNA; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; LAG3, lymphocyte-activation gene 3; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TME, tumour microenvironment.
Figure 3
Figure 3
Multiomic determinants of survival following tebentafusp. 1L, first line; 2L+, second line and beyond; ALP, alkaline phosphatase; CD163, M2 macrophage; CD8, cytotoxic T cell; CD3, T cell; ctDNA, circulating tumour DNA; IHC, immunohistochemistry; IL-6, interleukin-6; LDH, lactate dehydrogenase; mRNA, messenger RNA; NA, no data available to date; OS, overall survival; WES, whole exome sequencing.
Figure 4
Figure 4
Hypothesised circulating tumour DNA (ctDNA) and tumour microenvironment (TME) dynamics following tebentafusp. OS, overall survival.
See this image and copyright information in PMC

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