Immunotherapy for Kidney Cancer

Immunotherapy is the use of medicines to boost a person's own immune system to recognize and destroy cancer cells more effectively. Several types of immunotherapy can be used to treat kidney cancer.

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 “checkpoints,” which are proteins on immune cells 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, helping to restore the immune response against the cancer cells.

PD-1 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. By blocking PD-1, these drugs boost the immune response against kidney cancer cells. This can often shrink some tumors or slow their growth.

• For people whose cancer has been removed by surgery, but are at a higher risk of it coming back, pembrolizumab can be given for one year after surgery. It can also be given this way to people who have surgery to remove the main tumor along with surgery to remove a distant area(s) of cancer spread.

• Pembrolizumab can be used with the targeted drug axitinib as the first treatment for people with advanced kidney cancer.
• Pembrolizumab can also be used with the targeted drug lenvatinib as a first treatment in people with advanced kidney cancer.
• Nivolumab can be used for people whose advanced kidney cancer starts growing again after targeted drug treatments and has shown to help people live longer.
• For patients with intermediate or poor risk advanced kidney cancer who have not received any treatment, nivolumab can be given with ipilimumab (a CTLA-4 inhibitor) for 4 doses followed by nivolumab alone. This combination has been shown to help people live longer. Ipilimumab is discussed below. 
• For people with advanced kidney cancer, nivolumab might be used with the targeted drug cabozantinib as the first treatment. This combination has shown to help people live longer. 

Nivolumab is given as an intravenous (IV) infusion every 2, 3 or 4 weeks. Pembrolizumab is given every 3 or 6 weeks as an IV infusion.

Possible side effects of PD-1 inhibitors

Side effects of PD-1 inhibitors can include fatigue, cough, nausea, itching, skin rash, loss of appetite, constipation, joint pain, and diarrhea. See below for possible severe side effects of all checkpoint inhibitors.

PD-L1 inhibitors

Avelumab (Bavencio) targets PD-L1, a protein related to PD-1 that is found on some tumor cells and immune cells. Blocking the PD-L1 protein can help boost the immune response against cancer cells. This can often shrink some tumors or slow their growth.

Avelumab can be used with the targeted drug axitinib as the first treatment for people with advanced kidney cancer. It is given every 2 weeks as an IV infusion.

Possible side effects

The most common side effects of the combination avelumab with axitinib include fatigue, diarrhea, high blood pressure, skin rash or blistering, cough, shortness of breath, or abdominal pain. See below for possible severe side effects of all checkpoint inhibitors.

CTLA-4 inhibitors

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.

For patients with intermediate or poor risk advanced kidney cancer who have not received any treatment, ipilimumab can be given with nivolumab (a PD-1 inhibitor) for 4 doses followed by nivolumab alone.

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

Possible side effects of CTLA-4 inhibitors 

The most common side effects from ipilimumab include fatigue, diarrhea, skin rash, and itching. See below for possible severe side effects of all checkpoint inhibitors.

Possible serious side effects of all checkpoint inhibitors

More serious side effects occur less often, but are possible. These drugs work by removing the brakes on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious problems in the lungs, intestines, liver, hormone-making glands (like the thyroid), kidneys, or other organs. In some people these side effects can be life threatening.

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 that boost the immune system in a general way. Man-made versions of cytokines, such as interleukin-2 (IL-2) and interferon-alpha, are sometimes used to treat kidney cancer in very specific cases. Both cytokines can cause kidney cancers to shrink in a small percentage of patients.

Interleukin-2 (IL-2)

In the past, IL-2 was commonly used as first-line therapy for advanced kidney cancer, and it may still be helpful for some people. But it can cause serious side effects, so many doctors only use it for people who are healthy enough to tolerate the side effects and for cancers that aren’t responding to targeted drugs or other types of immunotherapy.

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. Special care is needed to recognize and treat these side effects. Because of this, high-dose IL-2 is only given in the hospital at certain centers that are experienced with giving this type of treatment. IL-2 is given through a vein (IV).

The possible side effects of high-dose IL-2 include:

These side effects are often severe and, rarely, can be fatal. Only doctors experienced in the use of these drugs should give this treatment.

Interferon-alfa

Interferon has less serious side effects than IL-2, but it does not seem to be as effective when used by itself. It is more often used in combination with the targeted drug bevacizumab (Avastin). Interferon is given as a subcutaneous injection (under the skin) usually three times a week.

Common side effects of interferon include flu-like symptoms (fever, chills, muscle aches), fatigue, and nausea.

• Extreme fatigue
• Low blood pressure
• Fluid buildup in the lungs
• Trouble breathing
• Kidney damage
• Heart attacks
• Intestinal bleeding
• Diarrhea or abdominal pain
• High fever and chills
• Rapid heart beat
• Mental changes