Immunotherapy and Targeted Drugs for Eye Cancer

Uveal (eye) melanoma that has spread outside of the eye can be hard to treat, and unfortunately standard chemotherapy drugs often are not very helpful.

In recent years, researchers have developed newer types of drugs to treat advanced melanomas. Several of these drugs are now used to treat melanomas of the skin, and some of them might be helpful in treating uveal melanomas as well. These newer drugs generally fall into 2 groups: immunotherapy and targeted drugs.

Immunotherapy

Immunotherapy drugs work to stimulate the body’s own immune system to help it recognize and attack cancer cells more effectively.

Bispecific T cell engager (BiTE)

Tebentafusp (Kimmtrak) is a type of immunotherapy know as a bispecific T cell engager (BiTE). Once it’s injected into the body, one part of the drug attaches to immune cells called T cells, while another part attaches to the gp100 protein on melanoma cells. This brings the two together, which helps the immune system attack the cancer cells.

Tebentafusp can be used to treat uveal melanoma that has spread or that can’t be treated with surgery, in people whose cells have a certain HLA tissue type (known as HLA-A*02:01). Before you get this treatment, your doctor will test you to see if you have this tissue type.

This drug is given as an IV infusion, typically once a week.

Common side effects of tebentafusp include:

  • Itching, rash, redness, and swelling of the skin
  • Fever
  • Feeling very tired
  • Headache
  • Nausea and vomiting
  • Belly pain
  • Swelling
  • Low blood pressure
  • Abnormal liver blood tests

Cytokine release syndrome (CRS) is a serious side effect that can occur when T cells in the body release chemicals (cytokines) that ramp up the immune system. This happens most often within the first day after the infusion, and it can be life-threatening. Symptoms can include:

  • High fever and chills
  • Severe nausea and vomiting
  • Trouble breathing
  • Feeling very tired
  • Feeling dizzy or lightheaded
  • Headache

Your health care team will watch you closely for possible signs of CRS, especially during and after the first few infusions. Be sure to contact your health care team right away if you have any symptoms that might be from CRS. 

Immune checkpoint inhibitors

Some immune cells have ‘checkpoint’ proteins that need to be turned on (or off) to start an immune response.  Melanoma cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs that target these checkpoint proteins can help restore the immune response, and some of these have been shown to be helpful in treating melanomas of the skin. Examples of immune checkpoint inhibitors include:

  • Pembrolizumab (Keytruda)
  • Nivolumab (Opdivo)
  • Ipilimumab (Yervoy) 

These drugs haven’t been shown to be quite as effective in treating uveal melanoma, but they might be helpful for some people.

For more on these medicines, see Immunotherapy for Melanoma Skin Cancer.

Targeted drugs

Some newer drugs target parts of melanoma cells that make them different from normal cells. For example, about half of all skin melanomas have a change (mutation) in a gene called BRAF, and several drugs that target this gene change are now available to treat these cancers. (See Targeted Therapy for Melanoma Skin Cancer.) This mutation isn't common in uveal melanomas, but in people whose cancer cells have it, these drugs might be helpful.

Drugs targeting other gene changes are also being studied.

For more information on some of these newer drugs, see What's New in Eye Cancer Research?

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Carvajal RD. Management of metastatic uveal melanoma.  UpToDate website. https://www.uptodate.com/contents/management-of-metastatic-uveal-melanoma. Updated March 19, 2018. Accessed August 27, 2018.

Finger PT. Chapter 116: Intraocular melanoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

Harbour JW, Shih HA. Initial management of uveal and conjunctival melanomas. UpToDate website. https://www.uptodate.com/contents/initial-management-of-uveal-and-conjunctival-melanomas. Updated Aug. 3, 2018. Accessed August 15, 2018.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Uveal Melanoma. V.2.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/uveal.pdf on January 26, 2022.

References

Carvajal RD. Management of metastatic uveal melanoma.  UpToDate website. https://www.uptodate.com/contents/management-of-metastatic-uveal-melanoma. Updated March 19, 2018. Accessed August 27, 2018.

Finger PT. Chapter 116: Intraocular melanoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

Harbour JW, Shih HA. Initial management of uveal and conjunctival melanomas. UpToDate website. https://www.uptodate.com/contents/initial-management-of-uveal-and-conjunctival-melanomas. Updated Aug. 3, 2018. Accessed August 15, 2018.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Uveal Melanoma. V.2.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/uveal.pdf on January 26, 2022.

Last Revised: January 26, 2022

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