Case Report: Long-term response to multimodal treatment in metastatic uveal melanoma.

BACKGROUND

Uveal melanoma (UM) is a rare intraocular malignancy with limited systemic treatment options and poor outcomes once metastatic. Tebentafusp, an ImmTAC (Immune-mobilizing monoclonal T-cell receptor Against Cancer) targeting gp100 in HLA-A*02:01-positive patients, has improved survival, although durable responses remain uncommon. Radiotherapy (RT) has been shown to induce immunogenic cell death and to modulate antitumor immune responses, supporting a potential synergistic interaction with systemic immunomodulatory therapies.

CASE PRESENTATION: We described a 39-year-old woman with localized UM initially treated with proton therapy (60 Gy in four fractions), who developed liver and hilar adenopathies metastases seven years later. After confirmation of metastatic melanoma and HLA-A*02:01 positivity, tebentafusp was started and well tolerated. Following four months of therapy, imaging revealed oligoprogression in a hilar adenopathy, while hepatic lesions remained stable. Stereotactic body radiotherapy (SBRT; 30 Gy in 10 fractions) was delivered to the nodal site while tebentafusp was continued. Subsequent MRI at nine months demonstrated partial response across all lesions. The patient has maintained disease control for an additional 35 months, with excellent quality of life (ECOG PS 0).

CONCLUSION

This case illustrates a durable systemic response after combined tebentafusp and SBRT, suggesting a synergistic interaction between ImmTAC-mediated T-cell activation and radiation-induced immunogenic modulation. Local RT may enhance antigen release and T-cell recruitment, amplifying tebentafusp efficacy and inducing abscopal-like effects. Prospective studies are warranted to evaluate this combination and identify biomarkers predictive of response.