Immunotherapy uses the immune system to attack kidney cancer. It can slow disease progression and shrink tumors in some cases.

There are several different types of immunotherapy that treat kidney cancer. Often, if one treatment does not work, a doctor may recommend a different therapy.

This article focuses on immunotherapy and reviews the different types, side effects, and more.

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Immunotherapy uses medications to help the immune system recognize and destroy cancer cells more efficiently.

There are two main types of immunotherapy that doctors use for kidney cancer. Within these types, doctors have several options to choose from and prescribe. The two types are immune checkpoint inhibitors and cytokines.

Doctors may use immunotherapies alone or in combination with other immunotherapies or treatments. A doctor can recommend them as a first- or second-line treatment.

However, in advanced stages of kidney cancer, immunotherapies pose a high risk of potentially serious side effects. A person can discuss their options with a doctor to determine the risks versus the benefits.

Read about immunotherapy vs. chemotherapy here.

Can it cure kidney cancer?

While immunotherapy cannot cure cancer, several studies have shown that it can help a person live progression-free for longer. Doctors may recommend immunotherapy for people living with advanced stage IV or recurrent cases of kidney cancers.

Learn more about kidney cancer here.

The American Cancer Society (ACS) provides the following information about immunotherapy drugs for kidney cancer:

NamesHow it worksWho it is forDoseSide effects
Immune checkpoint inhibitor:
PD-1 inhibitors
nivolumab (Opdivo) and pembrolizumab (Keytruda)This blocks PD-1 protein to boost an immune response against cancer cells. This can shrink a tumor or slow its growth.It is suitable for people living with advanced kidney cancer.Intravenous (IV) infusions every 2 to 6 weeksSide effects include:

• joint pain
• fatigue
• cough
• nausea
• diarrhea
• itching skin
• rash
• lack of appetite
• constipation
Immune checkpoint inhibitor:
PD-L1 inhibitors
avelumab (Bavencio)This blocks PD-L1 protein to boost an immune response against cancer cells. This can shrink a tumor or slow its growth.It is suitable for people living with advanced kidney cancer.IV infusions every 2 weeksSide effects include:

• high blood pressure
• fatigue
• skin rash
• diarrhea
• blistering skin
• cough
• abdominal pain
• shortness of breath
Immune checkpoint inhibitor:
CTLA-4 inhibitors
ipilimumab (Yervoy)This blocks CTLA-4, a protein on T-cells, to boost an immune response.It is suitable for people living with intermediate or advanced kidney cancer.Four treatments by IV infusion once every 3 weeks. Side effects include:

• itchiness
• skin rash
• fatigue
• diarrhea
Cytokine:
Interleukin-2
IL-2, Interleukin-2This is a small protein that boosts the immune system in general. People use it in combination with the targeted drug bevacizumab (Avastin).People who are healthy enough to tolerate the side effects and who are not responding to other drugs. This requires high doses, given in special centers.Side effects include:

• flu-like symptoms (chills, fever, fatigue, and confusion)
• nausea
• vomiting
• diarrhea
• low blood pressure
• abnormal heartbeat
• chest pain
• other heart problems
Cytokine:
Interferon-alfa
interferon-alfaThis is a small protein that triggers the immune system to attack the cancer cells. People use it in combination with the targeted drug bevacizumab (Avastin).People living with advanced kidney cancer.This is given as an injection under the skin 3 times per week.Side effects include:

• damage to kidneys
• extreme fatigue
• low blood pressure
• difficulty breathing
• fluid buildup in the lungs
• bleeding in intestines
• heart attacks
• high fever or chills
• diarrhea
• abdominal pain
• mental changes
• rapid heartbeat

The immune system relies on a complex system to help it identify potential threats as well as stop it from attacking normal, healthy cells. The immune system uses proteins on immune cells (which doctors call “checkpoints”) to trigger a response to a potential threat.

In some cases, cancerous kidney cells use the protein checkpoints to prevent an immune response that may destroy them. Immune checkpoint inhibitors prevent the cancer cells from deactivating or evading the immune cells.

In doing so, the medication helps the immune system recognize and then attack the cancerous cells.

There are several different types of immune checkpoint inhibitors that we describe in greater detail below.

PD-1 inhibitors

PD-1 inhibitors block a protein found on T-cells, a type of immune system cell. In doing so, they encourage the cells to attack the cancer cells.

Currently, there are two PD-1 inhibitors, nivolumab (Opdivo) and pembrolizumab (Keytruda).

Several groups of people may benefit from using this type of inhibitor, including:

  • people who have had surgical removal of a tumor with a high risk of recurrence
  • people living with advanced kidney cancer whose cancer starts growing again
  • people living with advanced kidney cancer, who may use nivolumab in combination with axitinib or lenvatinib as a first-line therapy
  • people living with advanced kidney cancer, who may use nivolumab with cabozantinib as a first-line therapy

Doctors administer both types of PD-1 inhibitors through intravenous (IV) infusion. A person receives nivolumab every 2 to 4 weeks, while doctors administer pembrolizumab every 3 or 6 weeks.

Possible side effects

Side effects can include:

PD-L1 inhibitors

PD-L1 is a protein that is similar to PD-1 and found on certain cancer and immune cells. Like other inhibitors, it blocks the protein and helps to activate the immune system against cancer cells. In doing so, it can help shrink the tumor or slow its growth.

Avelumab (Bavencio) currently has approval for use as a PD-L1 inhibitor in kidney cancer treatment.

Doctors may administer avelumab with a targeted drug, axitinib, as a first-line therapy to people living with advanced kidney cancer. A person will take it through IV infusion every 2 weeks.

Possible side effects

Potential side effects of PD-L1 inhibitors include:

CTLA-4 inhibitors

CTLA-4 inhibitors have a similar effect, boosting the immune system, but they work slightly differently. Rather than targeting a protein to encourage an immune response, this type of immunotherapy works by blocking a protein that limits a T-cell response.

In other words, it allows the T-cells to work by stopping certain cancer cells from turning them off.

Doctors may choose ipilimumab (Yervoy) for people living with intermediate or poor-risk advanced kidney cancer who have not received any other treatments.

Like with other inhibitors, a person receives an IV infusion. Doctors may give the treatment with nivolumab (a PD-1 inhibitor) for 4 sessions followed by nivolumab alone, and once every 3 weeks for 4 total treatments.

Possible side effects

Potential side effects include:

  • itchiness
  • skin rash
  • fatigue
  • diarrhea

Serious side effects of checkpoint inhibitors

Checkpoint inhibitors all pose a risk of causing serious side effects. A person should discuss the risk with a doctor prior to starting treatment.

According to the ACS, these medications work by taking away the brakes on the immune system. This can cause or allow the immune system to start attacking other organs and systems in the body, which can become life threatening.

Organs and systems that this may affect include the:

Doctors prescribe high-dose steroids when immunotherapy affects other organs and systems in the body. It is important for a person not to take any steroids other than those a doctor prescribes. Steroids suppress the immune system, whereas immunotherapy aims to boost it.

If a person experiences any symptoms that suggest inflammation, they should contact their oncologist.

Cytokines are a type of small protein that boost the immune system. They can help abnormal cells die and keep healthy cells alive for longer.

There are two man-made versions of cytokines that doctors use to treat kidney cancer. They include interleukin-2 and interferon-alfa.

Interleukin-2 (IL-2)

IL-2 was previously a first-line therapy for people living with advanced kidney cancer. However, it has several potential side effects, which made doctors reconsider its use.

Doctors now typically only give high doses of IL-2 to people who are healthy enough to handle the potential side effects. When a person takes it in high doses, it can help shrink tumors.

Due to the potential for serious side effects, doctors only administer it in specialized hospital settings or care centers. A doctor will give the medication through a vein and monitor the person for potential side effects.

Side effects

Side effects can be severe and life threatening in some cases. Some potential side effects include:

  • flu-like symptoms — chills, fever, fatigue, and confusion
  • nausea
  • vomiting
  • diarrhea
  • low blood pressure
  • abnormal heartbeat
  • chest pain
  • other heart problems

Interferon-alfa (INF-alfa)

INF-alfa is another type of cytokine that doctors use to treat kidney cancer. Doctors prescribe it in combination with a targeted drug called bevacizumab.

This type of cytokine has less serious side effects than IL-2, but it is also less effective overall.

Doctors give this medication as an injection under the skin 3 times per week.

Side effects

Some possible side effects include:

  • damage to kidneys
  • extreme fatigue
  • low blood pressure
  • difficulty breathing
  • fluid buildup in the lungs
  • intestinal bleeding
  • heart attacks
  • high fever or chills
  • diarrhea
  • abdominal pain
  • mental changes
  • rapid heartbeat

Treatments for kidney cancer can vary according to several factors. Age, overall health, and the cancer stage can influence which treatments a doctor recommends.

For stages I–III, surgery can often cure kidney cancer. For advanced stage IV cancer, immunotherapy may provide a better option either alone or in combination with other therapies. It can slow disease progression and, in some cases, shrink a tumor.

Research points to the potential use of immunotherapies, such as PD-1, for advanced clear cell renal cell carcinoma, the most common form of kidney cancer.

However, a person should talk with a doctor about the potential benefits of immunotherapy to make sure it could work for them.

Overall success rates for immunotherapies are difficult to summarize, but around 15–20% of people experience lasting results from immunotherapy.

According to the National Cancer Institute (NCI), using immunotherapies in combination with targeted therapies may work best for advanced cases of kidney cancer.

One 2018 trial reported promising effects of a combination treatment of the immune checkpoint inhibitors nivolumab and ipilimumab, followed by nivolumab alone as a maintenance therapy.

After 18 months of treatment, 75% of patients on the immunotherapy combination were still alive, compared with 60% who had sunitinib alone. Of the patients using combination immunotherapy:

  • 42% experienced a tumor response, versus 27% in the sunitinib group
  • 9% experienced a complete response, meaning their cancer was no longer detectable, versus 1% in the sunitinib group
  • 46% experienced serious side effects, versus 63% in the sunitinib group
  • 22% discontinued treatment because of side effects, versus 12% in the sunitinib group

People who undergo immunotherapy often experience periods of progression-free survival. This means that the cancer did not grow or spread during a certain period of time.

A person should discuss the probable progression-free time frames of a medication when talking about immunotherapy as an option with a doctor.

Learn about kidney cancer outlook here.

When taking immunotherapy, a person may experience side effects that range from mild to potentially life threatening. A person should talk with their doctor if they notice any new or changing side effects during treatment.

Some complementary therapies may help a person manage side effects. A person may wish to discuss options with a doctor prior to starting any management therapies. Possible complementary therapies that may help include:

Researchers continually look into new treatment methods and ways to improve existing treatments. Clinical trials are a type of research that tests the safety and effectiveness of new medications or new uses for existing medications.

The goal of clinical trials is to determine if a new treatment will provide better or safer benefits to a larger number of people.

A person interested in joining a clinical trial can talk with a doctor. They may have information on local trials.

A person can also check the NCI’s website for new or ongoing clinical trials.

This section offers answers to some frequently asked questions about immunotherapy for kidney cancer.

Does the stage of kidney cancer influence how effective immunotherapy is?

Several factors can affect kidney cancer treatments. Evidence suggests that while immunotherapy can help a person live longer, it may not be appropriate for all types of kidney cancer.

What happens if immunotherapy doesn’t work?

Doctors have several potential treatments to choose from. Often, if one does not work, they can try another or combine the therapy with another medication for better success.

How long does immunotherapy take to work?

Immunotherapy will work faster for some people than for others. A person’s doctor will schedule regular checkups to look for tumor shrinkage, assess side effects, and answer questions. If a person’s tumor shrinks, immunotherapy is working.

Immunotherapy is a type of cancer therapy that uses the body’s immune system to fight cancer cells. Not everyone is a good candidate for immunotherapy because it can cause serious side effects.

The main types of immunotherapy doctors prescribe for kidney cancer are immune checkpoint inhibitors and cytokines.

While surgery is often successful in curing early stage cancers, immunotherapy is often a better option for treating advanced kidney cancer as it can slow disease progression.

A person with kidney cancer can talk with a doctor about the benefits and drawbacks of immunotherapy.