Immunotherapy for Small Intestine Cancer (Adenocarcinoma)

Immunotherapy is the use of medicines to help a person’s own immune system better recognize and destroy cancer cells.

When is immunotherapy used?

Immunotherapy is now used to treat advanced-stage small intestine cancer if the cancer cells have either of these findings:

• Changes in mismatch repair genes (dMMR) that affect the cells’ ability to fix those mistakes
• High levels of microsatellite instability (MSI-H), meaning the cancer cells have many DNA copying mistakes

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking the body’s normal cells. To do this, it uses “checkpoints” – proteins on immune cells that need to be turned on (or off) to start an immune response. Intestinal cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs that target these checkpoints help restore the immune response against intestinal cancer cells.

Drugs called checkpoint inhibitors can be used if the cancer cells have tested positive for specific gene changes, specifically a high level of microsatellite instability (MSI-H), or changes in one of the mismatch repair (MMR) genes.

These drugs might be used for cancers that can’t be removed with surgery, have come back (recurred) after treatment, or have spread to other parts of the body (metastasized).

PD-1 inhibitors

Pembrolizumab (Keytruda), nivolumab (Opdivo), cemiplimab (Libtayo), retifanlimab (Zynyz), dostarlimab (Jemperli), tislelizumab (Tevimbra), and toripalimab (Loqtorzi) are drugs that target PD-1, a protein on immune system cells called T cells. This protein normally helps keep T cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against cancer cells. They are only given if the tumor has findings of dMMR or MSI-H.

Pembrolizumab can be given alone. It is given as an intravenous (IV) infusion every 3 or 6 weeks.

Nivolumab can be given alone or with ipilimumab (see below). It can be given by itself as an IV infusion every 2 or 4 weeks. If it is used along with ipilimumab, then it is typically given every 3 weeks.

Dostarlimab can be given alone. It is given as an intravenous (IV) infusion every 3 weeks for 4 treatments and then given at a higher dose every 6 weeks.

CTLA-4 inhibitor

Ipilimumab (Yervoy) is another drug that boosts the immune response. It blocks CTLA-4, another protein on T cells that normally helps keep them in check.

This drug can be used along with nivolumab (Opdivo) to treat small intestine cancer. It is given as an intravenous (IV) infusion, usually once every 3 weeks for 4 treatments.

Possible side effects of immunotherapy

Side effects of these drugs include fatigue, cough, nausea, diarrhea, skin rash, loss of appetite, constipation, joint pain, and itching.

Other, more serious side effects occur less often.

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 right away if you have any of these symptoms while getting these drugs.

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

It’s very important to report any new side effects during or after treatment with any of these drugs to your health care team promptly. If serious side effects do occur, you may need to stop treatment and take high doses of corticosteroids to suppress your immune system.