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Immunotherapy uses medicines to help a person’s immune system better recognize and destroy cancer cells. Many types of immunotherapy are being tested in clinical trials, and some are used to treat vaginal cancer.

Immune checkpoint inhibitors

An important part of a person's immune system is its ability to keep itself from attacking the body's normal cells. To do this, it uses 'checkpoint' proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Drugs that target these checkpoints (called immune checkpoint inhibitors) can be used to treat some vaginal cancers. PD-1 proteins are on the immune cells; PD-L1 checkpoints are on the tumor cells.

PD-1 inhibitors

PD-1 is a checkpoint protein on immune system cells called T cells. PD-1 normally helps keep T cells from attacking other cells in the body (including some cancer cells). By blocking PD-1, these drugs boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

Pembrolizumab (Keytruda) can be used along with the chemotherapy drugs cisplatin/carboplatin and paclitaxel with or without bevacizumab to treat vaginal cancer that has spread to other parts of the body.

Pembrolizumab can also be used by itself to treat some advanced vaginal cancers. It is typically used after other treatments have been tried, if there are no other good treatment options, and if the cancer cells have been tested and have any of the following:

• A high level of microsatellite instability (a lot of gene changes in a short, repeated sequence of DNA) or a defect in a mismatch repair gene (dMMR)
• A high tumor mutational burden (TMB-H), meaning the cells have many gene mutations
• PD-L1 positive, meaning the cancer cells have a high amount of the PD-L1 protein on their surface.

This drug is given as an intravenous (IV) infusion, typically once every 3 or 6 weeks.

Nivolumab (Optivo) can be used to treat advanced vaginal cancers after other treatments have been tried if the tumor cells are PD-L1 positive. It is given as an IV infusion, typically once every 2 weeks.

Cemiplimab (Libtayo) was studied in people with cervical cancer. Since vaginal cancer is relatively uncommon, chemo drugs approved for cervical cancer are commonly used to treat vaginal cancer as well.

It can be given to patients with advanced vaginal cancer that recurred (came back) after initial systemic treatment, regardless of their PD-L1 status. This drug is given as an IV infusion, typically once every 3 weeks.

Possible side effects of immune checkpoint inhibitors

Side effects of PD-1 inhibitors can include:

• Feeling tired or weak
• Fever
• Cough
• Nausea
• Itching
• Skin rash
• Loss of appetite
• Muscle or joint pain
• Shortness of breath
• Constipation or diarrhea

Other, more serious side effects occur less often. These can include:

Infusion reactions: Some people might have an infusion reaction while getting these drugs. This is like an allergic reaction and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting this drug.

Autoimmune reactions: These drugs work by removing one of the safeguards on the body’s immune system. Sometimes this allows the immune system to attack other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.

It’s very important to report any new side effects to your health care team right away. If you have a serious side effect, treatment may need to be delayed or stopped, and you may be given high doses of corticosteroids to suppress your immune system.