Uveal melanoma is an aggressive disease without effective adjuvant
therapy for
metastases. Despite genomic differences between cutaneous and uveal
melanomas,
therapies based on shared
biological factors could be effective against both
tumor types. High expression of
glycoprotein-NMB (GPNMB) in cutaneous
melanomas led to the development of
CDX-011 (
glembatumumab vedotin), a fully human
monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin
monomethylauristatin E. Ongoing phase II trials suggest that
CDX-011 has activity against advanced cutaneous
melanomas. To determine the potential role of
CDX-011 in uveal
melanomas, we studied their GPNMB expression.
Paraffin-embedded tissues from 22 uveal
melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated
CDX-011 (unconjugated) antibody.
Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high
melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21
tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of
tumor cells with variable intensity (5
tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18
tumors (61.1%) expressed GPNMB in >or=50% of cells. Spectral imaging showed diffuse
CDX-011 (unconjugated) reactivity in the remaining case.
Uveal melanoma, like cutaneous
melanoma, commonly expresses GPNMB. Ongoing clinical trials of
CDX-011 should be extended to patients with metastatic
uveal melanoma to determine potential efficacy in this subset of patients with
melanoma.