36 | Neoadjuvant strategy for locally advanced conjunctival melanoma: a single-center approach to eye preservation

F. Rifaldi^1|2, M. Angi³, L. Giuseppe¹, F. Lanza³, A. Spagnoletti¹, J. Sergenti³, A. Indini¹, E. Mastrogiuseppe³, M. Del Vecchio¹, L. Di Guardo¹ | ¹Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; ²Fondazione IRCCS Policlinico San Matteo, Pavia; ³Ocular Oncology Service, Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background: Conjunctival melanoma is a rare but aggressive ocular tumor with high metastatic potential leading to 30% mortality rate. Standard treatment relies on surgery and brachytherapy, but local recurrence and mutilating procedures (e.g., exenteration) are common. Molecular profiling reveals similarities with cutaneous melanoma (e.g., BRAF, NRAS, NF1 mutations), supporting use of targeted and immune therapies. Neoadjuvant systemic therapy may enhance resectability, preserve the eye and improve EFS and systemic disease control.

Methods: Four patients with locally advanced conjunctival melanoma who refused radical surgery were treated between June 2024 and June 2025. All patients underwent molecular profiling (BRAF, PD-L1 or NGS) to guide treatment selection. Three received neoadjuvant immunotherapy: two (Figure 1) with ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg), and one with single-agent nivolumab (480 mg every 4 weeks); one BRAF V600E-mutated melanoma patient received targeted therapy with dabrafenib and trametinib. All patients underwent radiological staging before surgery, followed by regular clinical and radiologic follow-up.

Results: Three patients underwent complete tumor resection with ocular preservation (Figure 1). One patient achieved a complete response to neoadjuvant immunotherapy (Nivolumab), for which surgery defferal is being considered. No patient required exenteration. All treatments were well tolerated, with only grade 1–2 immune-related adverse events. At the last follow-up (May2025), all patients were alive, and three of them were disease-free with no distant metastases were observed.

Conclusions: Neoadjuvant systemic therapy is both safe and feasible for treating conjunctival melanoma, with treatment being personalized according to molecular profiling of the tumor. Given the disease’s rarity, a multidisciplinary approach is essential for effective management, and this strategy can help avoid exenteration while improving surgical outcomes. However, prospective studies are necessary to determine the optimal protocols and criteria for patient selection.

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Figure 1.