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Histologically, uveal melanoma (UM) and cutaneous melanoma (CM) may look similar, but they are actually unique diseases.
While treatment options for UM are limited, patients should be referred to a multidisciplinary team for consideration of available systemic options.1,12,13
The differences in oncogenic drivers and immunogenicity between UM and CM result in distinct mechanisms of disease.
UM | CM |
---|---|
GNAQ/GNA11 | BRAF |
SF3B1 | NRAS |
EIF1AX | MEK1/2 |
CYSTLR2 | PIK3CA |
PLCβ4 | PIK3CG |
AKT1/AKT3 | |
RAC1 | |
KIT |
Because CM has a high incidence of BRAF mutations, effective treatment options for CM include anti-BRAF and anti-MEK therapies.
Immunotherapy has increasingly become the latest pillar of systemic therapy in oncology, and the recent approvals of checkpoint inhibitors for CM have served as breakthrough options for many patients.3 Unfortunately, these therapies have not demonstrated the same efficacy in the treatment of UM.3,12,14
In addition to having different oncogenic drivers, UM and CM have distinct mutation burdens.3,15
Disease | Mutations/Mb |
---|---|
Skin squamous cell carcinoma | |
Skin melanoma | |
Lung squamous cell carcinoma | |
Brain glioblastoma | |
Eye intraocular melanoma | |
Bone marrow myelodysplastic syndrome | |
The immune tumor microenvironment factors into the distinction between UM and CM. While CM contains adequate numbers of effector T cells and is inflamed (“hot”), the effector T cells surrounding UM are limited to the tumor periphery (immunologically “cold”).14-18
PD-L1 expression differs significantly between metastases of UM and those of CM. Only 5.1% (4 of 78) of metastatic UM specimens expressed PD-L1 in comparison to 26.1% (77 of 295) of metastatic CM specimens.14
I was diagnosed with ocular cancer 4 years ago; I can remember the exact day like it was just yesterday. I went in for my annual eye exam feeling like there was a hair in my eye. Then I started seeing a light in my left eye and it was to the left, diagonal, coming at me from the top.
My optometrist didn’t see anything out of the norm. He just said it would work its way out. Over the next 3 months, the sensation continued to get worse. He finally referred me to a retina specialist—who dilated my eye and immediately noticed a “mole” on the back of it.
About a week later I started radiation, and then six and a half weeks later they said it didn’t work. On December 3rd, my eye was removed.
I am grateful for the care that I have received over the past several years. I just wished there was more information about this rare disease. More people need to be aware of the symptoms and what to do about it.
— Patient with UM
In 2010 I had what looked like a pencil eraser on top of my head. I didn’t really think much of it—and just continued to shave around it. My wife was the one that encouraged me to get it looked at.
I was familiar with skin cancer but mine didn’t look like anything on the Internet. It came back positive as melanoma and I quickly had it surgically removed.
Within 6 months, I learned the cancer metastasized to my liver. Fortunately, I qualified for a clinical study and I have a wonderful treatment team that cared for me.
It’s one of those things; you never think it can happen to you. But I feel fortunate that there are new treatments that are helping people like me live longer.
— Patient with CM
Number of available clinical trials as of August 2019.
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