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Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. 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. Kidney cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. But these drugs target the checkpoint proteins, which helps the immune system attack the cancer cells.

PD-1 and PD-L1 inhibitors

Pembrolizumab (Keytruda) and Nivolumab (Opdivo) 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. Avelumab (Bavencio) targets PD-L1, a protein that binds to PD-1 that is found on some tumor cells and immune cells. By blocking either of these checkpoint proteins, these drugs boost the immune response against kidney cancer cells. This can often shrink tumors or slow their growth.

These drugs can be used in different situations to treat kidney cancer:

• Pembrolizumab can be given as an adjuvant treatment after surgery in people who are at higher risk of their cancer coming back, to help lower this risk. It is usually given for about a year after surgery.
• One of these drugs is often part of the first treatment for advanced kidney cancer, along with a targeted drug or with the CTLA-4 inhibitor ipilimumab (see below).
• One of these drugs can also be used if advanced kidney cancer starts growing again after other drug treatments have been tried. It might be given alone or along with another type of drug.

These drugs are given by infusion into a vein (IV), typically once every 2 to 6 weeks, depending on the drug.

Possible side effects of PD-1 and PD-L1 inhibitors

The most common side effects of these drugs include:

• Fatigue (feeling tired)
• Cough
• Nausea
• Itching
• Skin rash
• Loss of appetite
• Constipation
• Joint pain
• Diarrhea

See below for possible severe side effects of all checkpoint inhibitors. While it’s not common, these drugs can also have more serious side effects - see below.

CTLA-4 inhibitor

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

Ipilimumab is not used by itself, but with nivolumab (a PD-1 inhibitor – see above).

Ipilimumab is given by intravenous (IV) infusion, usually once every 3 weeks for 4 treatments.

Possible side effects of CTLA-4 inhibitors 

Side effects tend to be more common with this drug than with the PD-1 and PD-L1 inhibitors discussed above. The most common side effects from ipilimumab include:

• Fatigue
• Diarrhea
• Skin rash
• Itching

This drug can also have more serious side effects - see below.

Possible serious side effects of all checkpoint inhibitors

Serious side effects aren’t common with these drugs, but they are possible.

Infusion reactions: Some people might have an infusion reaction while getting one of 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 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 (like the thyroid), kidneys, or other organs.

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

Cytokines

Cytokines are small proteins in the body that boost the immune system. Man-made versions of cytokines, such as interleukin-2 (IL-2), might sometimes be used to treat kidney cancer in very specific cases. They can shrink kidney cancers in a small percentage of people.

Interleukin-2 (IL-2)

In the past, IL-2 was often used as a first-line treatment for advanced kidney cancer, and it may still be helpful for some people. But the newer immune checkpoint inhibitors (see above) and targeted drugs are more likely to be helpful.

IL-2 is given by infusion through a vein (IV). Giving high doses of IL-2 seems to offer the best chance of shrinking the cancer, but this can cause serious side effects, so it is not used in people who are in poor overall health.

Side effects of IL-2 can include flu-like symptoms, such as fever, chills, aches, severe tiredness, drowsiness, and low blood cell counts. In high doses, IL-2 can cause fluid to build up in the body so that the person swells up and can feel very sick.

Because these side effects can be severe, high-dose IL-2 is only given in the hospital at certain centers that are experienced with giving this type of treatment.