Immunotherapy for Colorectal Cancer

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

Immune checkpoint inhibitors

For people with either early- or advanced-stage colorectal cancer, immunotherapy is now a cornerstone of treatment if the tumor has findings of dMMR (deficient mismatch repair) or MSI-H (microsatellite instability-high).

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. Colorectal cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs that target these checkpoints help to restore the immune response against colorectal cancer cells.

Drugs called checkpoint inhibitors can be used for people whose colorectal 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 given to people before surgery for early-stage colon cancer, or to treat people whose cancer can’t be removed with surgery, has come back (recurred) after treatment, or has spread to other parts of the body (metastasized).

PD-1 inhibitors

Pembrolizumab (Keytruda), nivolumab (Opdivo), and Dostarlimb (Jemperli) are drugs that target PD-1, a protein on immune system cells called T cells that normally help keep these cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against colorectal cancer cells. They are only given if the tumor has had 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 is typically 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. This drug is not approved specifically to treat colorectal cancer at this time. It is approved to treat other types of cancer, but doctors can prescribe it off-label for colorectal cancer. Still, it’s important to check with your insurance provider before getting this drug to make sure it is covered.

CTLA-4 inhibitor

Ipilimumab (Yervoy) is another drug that boosts the immune response, but it has a different target. 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 colorectal cancer, but it’s not used alone. 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, kidney, 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.