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Updated: Sep 30, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Genetic characterization of advanced conjunctival melanoma and response to systemic treatment
Georg C Lodde1, Philipp Jansen1, Inga Möller1
1Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
Background:
Conjunctival melanoma is a rare type of ocular melanoma, which is prone to local recurrence and metastasis and can lead to patient death. Novel therapeutic strategies have revolutionized cutaneous melanoma management. The efficacy of these therapies in conjunctival melanoma, however, has not been evaluated in larger patient cohorts.
Methods:
In this multi-center retrospective cohort study with additional screening of the ADOREG database, data were collected from 34 patients with metastatic conjunctival melanoma who received targeted therapy (TT) (BRAF ± MEK inhibitors) or immune checkpoint inhibitors (ICI) (anti-PD-1 ± anti-CTLA4). In 15 cases, tissue was available for targeted next-generation-sequencing (611 genes) and RNA sequencing. Driver mutations, tumor mutational burden, copy number variations and inflammatory/IFNγ gene expression signatures were determined.
Results:
Genetic characterization identified frequent BRAF (46.7%, 7/15), NRAS (26.7%, 4/15), NF1 (20%, 3/15), and TERT promoter (46.7%, 7/15) mutations. UV associated C>T and CC>TT mutations were common. Median follow-up time after start of first TT or ICI therapy was 13.2 months. In 26 patients receiving first-line ICI, estimated one-year progression-free survival (PFS) rate was 42.0%, PFS and overall survival (OS) 6.2 and 18.0 months, respectively. First-line TT was given to 8 patients, estimated one-year PFS rate was 54.7%, median PFS and OS 12.6 and 29.1 months, respectively.
Conclusions:
Our findings support the role of UV irradiation in conjunctival melanoma and the genetic similarity with cutaneous melanoma. Conjunctival melanoma patients with advanced disease benefit from both targeted therapies (BRAF ± MEK inhibitors) and immune checkpoint inhibitors.
Insights
Metastatic conjunctival melanoma patients benefit from targeted therapies (TT) and immune checkpoint inhibitors (ICI). Genetic analysis reveals similarities to cutaneous melanoma, supporting UV radiation
Area of Science:
- Ophthalmology
- Oncology
- Genetics
Background:
- Conjunctival melanoma is a rare, aggressive ocular cancer with high recurrence and metastasis rates.
- Novel therapies have improved cutaneous melanoma outcomes, but their efficacy in conjunctival melanoma requires evaluation.
- Limited data exists on advanced conjunctival melanoma treatment responses.
Purpose of the Study:
- To evaluate the efficacy of targeted therapy (TT) and immune checkpoint inhibitors (ICI) in metastatic conjunctival melanoma.
- To characterize the genetic landscape of conjunctival melanoma.
- To compare treatment outcomes between TT and ICI.
Main Methods:
- Multi-center retrospective cohort study including 34 metastatic conjunctival melanoma patients.
- Patients received either TT (BRAF ± MEK inhibitors) or ICI (anti-PD-1 ± anti-CTLA4).
- Targeted next-generation sequencing and RNA sequencing were performed on 15 tumor samples.
Main Results:
- Frequent mutations included BRAF (46.7%), TERT promoter (46.7%), NRAS (26.7%), and NF1 (20%).
- UV-associated mutations (C>T, CC>TT) were common, indicating UV's role.
- One-year progression-free survival (PFS) rates were 42.0% for ICI and 54.7% for TT; median OS was 18.0 months (ICI) and 29.1 months (TT).
Conclusions:
- Conjunctival melanoma shares genetic similarities with cutaneous melanoma, with UV radiation playing a significant role.
- Advanced conjunctival melanoma patients demonstrate clinical benefit from both TT and ICI.
- TT showed a trend towards longer PFS and OS compared to ICI in this cohort.
