Immunotherapy for Gallbladder Cancer

Immunotherapy is the use of 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 gallbladder cancer.

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 “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 gallbladder cancers.

PD-1 inhibitors

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs that target PD-1, 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, this drug boosts the immune response against cancer cells. This can shrink some tumors or slow their growth.

These drugs can be used in different ways to treat gallbladder cancer:

• Pembrolizumab (Keytruda) with chemotherapy: This drug can be given along with the chemo drugs gemcitabine and cisplatin to treat gallbladder cancer that can’t be removed by surgery or that has spread to other parts of the body.
• Pembrolizumab (Keytruda) alone: This drug might be used if your tumor has a high number of specific gene changes (a high level of microsatellite instability or MSI-H), if there is a defect in a mismatch repair gene (dMMR), or if your tumor cells have a generally high number of gene changes (a high tumor mutational burden or TMB-H).
• Nivolumab (Opdivo) with ipilimumab (Yervoy): These drugs might be used together if your tumor cells have a high number of gene mutations (a high mutational burden or TMB-H).

These drugs are given as an intravenous (IV) infusion, typically once every 2 or 6 weeks.

PD-L1 inhibitor

Durvalumab (Imfinzi) is a drug that targets PD-L1, a protein related to PD-1 that is found on some tumor cells and immune cells. Blocking this protein can help boost the immune response against cancer cells.

This drug can be used along with the chemotherapy drugs gemcitabine and cisplatin to treat gallbladder cancer that can’t be removed by surgery or that has spread to other parts of the body.

This drug is given as an intravenous (IV) infusion, typically every 2 to 4 weeks.

CTLA-4 inhibitor

Ipilimumab (Yervoy) is another checkpoint inhibitor, but it has a different target. It blocks CTLA-4, another protein on T cells that normally helps keep them in check.

It might be used with Nivolumab (Opdivo) to treat gallbladder tumors that have a high mutational burden (TMB-H).

This drug is given as an intravenous (IV) infusion, usually once every 3 weeks

Possible side effects of immune checkpoint inhibitors

Some of the more common side effects of these drugs can include fatigue, cough, nausea, skin rash, poor appetite, constipation, joint pain, and diarrhea.

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

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

It’s very important to report any new side effects to someone on your health care team as soon as possible. If serious side effects do occur, treatment may need to be stopped and you might be given high doses of corticosteroids to suppress your immune system.