Understanding Immunotherapy for Kidney Cancer

The main types of immunotherapy used specifically for kidney cancer include:

• immune checkpoint inhibitors, such as CTLA-4, PD-1, and PD-L1 inhibitors
• cytokines, such as interleukin-2 and interferon-alfa

Learn more about each type and the possible side effects of each below.

CTLA-4 inhibitors

CTLA-4 inhibitors belong to a group of immunotherapy treatments called immune checkpoint inhibitors.

Checkpoints are types of proteins on cells that help deliver immune responses. Immune checkpoint inhibitors ensure that all checkpoints are working to protect healthy cells against cancerous ones.

Your doctor may recommend CTLA-4 inhibitors to help block proteins of the same name. These usually develop on T-cells.

Ipilimumab (brand name Yervoy) is a CTLA-4 inhibitor used for kidney cancer.

It may be used as a combination treatment with other immune checkpoint inhibitors. This therapy is delivered via intravenous (IV) infusions for up to four times total, with 3 weeks in between treatments.

Side effects from CTLA-4 inhibitors may include:

• fatigue
• skin rashes
• itchy skin
• diarrhea

PD-1 inhibitors

PD-1 is another type of immune checkpoint inhibitor that also targets T-cells.

Two options include nivolumab (Opdivo) and pembrolizumab (Keytruda), which are both delivered via IV spaced weeks apart.

PD-1 may help slow the growth of kidney cancer cells and expose tumor cells to immune system targeting and death, which may decrease tumor size.

Side effects may include:

• fatigue
• loss of appetite
• constipation or diarrhea
• nausea
• itchy skin or rash
• joint pain
• coughing
• anemia
• liver abnormalities

PD-L1 inhibitors

PD-L1 is a protein found in some cancer cells. By blocking this protein with PD-L1 inhibitors, the immune system may help shrink or stop further cancerous growths.

Avelumab (Bavencio) is a type of PD-L1 inhibitor used for kidney cancer that’s also delivered though IV treatments. This medication is administered every 2 weeks and may be combined with other medications.

Possible side effects include:

• fatigue
• abdominal pain
• diarrhea
• high blood pressure (hypertension)
• breathing difficulties
• skin blisters or rashes
• musculoskeletal pain

Interleukin-2 (IL-2) cytokines

IL-2 is a high-dose cancer treatment that’s administered via IV. Due to a high risk of side effects, it’s typically only used in advanced kidney cancer that hasn’t responded to other types of immunotherapy.

Aldesleukin (Proleukin) is an example of a cytokine that targets the IL-2/IL-2R pathway.

IL-2 is just one class of cytokines sometimes used to treat kidney cancer. Cytokines are types of proteins that may help boost the immune system, possibly shrinking or killing cancer cells and decreasing tumor size.

Your doctor will consider whether you are in good enough health to tolerate the side effects. Such effects may include:

• kidney damage
• low blood pressure (hypotension)
• rapid heart rate
• heart attack
• intestinal bleeding
• gastrointestinal concerns
• breathing difficulties
• mental changes
• high fever, sometimes accompanied by chills
• fluid buildup in the lungs
• extreme fatigue

Interferon-alfa cytokines

Interferon-alfa is another type of cytokine treatment that may be an alternative to IL-2. The downside is that this treatment may not be effective in treating kidney cancer alone.

In fact, your doctor may use it as part of a combination drug, which is injected under your skin three times per week.

Side effects from interferon-alfa treatment may include:

• fatigue
• fever and chills
• nausea
• muscle aches

Stages 1, 2, and 3 are considered early forms of kidney cancer. Most of these cases may be treated with surgery.

If you have stage 4, or more advanced kidney cancer, your doctor may recommend immunotherapy. This type of treatment is also used in recurrent cancers.

While the aforementioned immunotherapies may be used for stage 4 kidney cancer, there are some limitations and combination therapies that may be considered. These include:

• IL-2 cytokines, which are only typically used if your doctor determines the possible benefits outweigh the high risk of side effects
• PD-L1 inhibitor combination therapies, specifically avelumab and a targeted therapy called axitinib (Inlyta)
• PD-1 inhibitor combination therapies, such as nivolumab used with another type of targeted therapy called cabozantinib (Cabometyx)

Overall, researchers believe that immune checkpoint inhibitors —particularly PD-1 — may be helpful for advanced clear cell renal cell carcinoma (ccRCC).

However, these inhibitors may produce the opposite effect in advanced kidney cancer.

There are many different types of immunotherapy, so it’s difficult to give an estimate of the overall success rates for treatment. However, research has helped to reveal some trends that may improve treatment outlook.

For example, combination therapies that use immunotherapy with a targeted therapy are thought to be more successful in treating advanced kidney cancer than using each treatment individually.

Several studies have demonstrated that combining treatments can improve progression-free survival, the amount of time that patients go without their disease worsening.

Many of these trials compare combination immunotherapy treatments to targeted therapy with a tyrosine kinase inhibitor (TKI) medication called sunitinib (Sutent), which discourages tumor growth.

Sunitinib has been used as a first-line therapy for advanced kidney cancer since 2006.

For example, a 2018 study found that combining nivolumab and ipilimumab led to a 75 percent survival rate at 18 months, compared with a 60 percent rate when using sunitinib alone.

Of the 1,096 patients, the median progression-free survival was 11.6 months with the combination and 8.4 months with sunitinib.

A 2019 study, funded by Pfizer, paired avelumab plus axitinib in comparison with sunitinib.

Among the 866 patients, the median progression-free survival was 13.8 months with the combination therapy, as compared with 8.4 months with the single treatment.

Another 2019 study, funded by Merck, combined pembrolizumab and axitinib in comparison with sunitinib.

Among the 861 patients, the median progression-free survival was 15.1 months in the pembrolizumab/axitinib group and 11.1 months in the sunitinib group.

IL-2 and interferon-alfa cytokines are thought to possibly shrink kidney cancer cells in only a small percentage of people. As such, cytokine treatment is reserved for cases where other immunotherapies don’t work.

Due to the way they modify your immune system’s responses, checkpoint inhibitors may sometimes send your immune system into overdrive, leading to organ damage. Possible affected areas may include the:

• liver
• lungs
• kidneys
• intestines
• thyroid gland

To minimize side effects in these areas of the body, your doctor may prescribe oral corticosteroids.

These immunosuppressants are sometimes used in place of traditional immunotherapy for kidney cancer if you don’t respond well to these types of therapies.

Report any new side effects from immunotherapy to your doctor right away. You may also consider talking with them about complementary medical approaches to help manage existing side effects, such as:

• biofeedback
• meditation and yoga
• acupuncture
• massage or reflexology
• herbs, vitamins, or botanicals
• diets

Research in the areas of kidney cancer development, diagnosis, and treatment are ongoing.

Recent clinical trials have also looked at the efficacy of immunotherapies for kidney cancer, along with the combinations with targeted drugs such as axitinib and cabozantinib.

Once the safety of new treatments has been tested in a clinical setting, the FDA may approve future kidney cancer therapies.

You may also consider talking with your doctor about the possibility of participating in clinical trials. The National Cancer Institute’s current list of clinical trials for kidney cancer treatment may be found here.

Immunotherapy may treat kidney cancer by changing the way your immune system responds to cancerous cells. These come in the form of immune checkpoint inhibitors or cytokines.

Sometimes, immunotherapy may be combined with targeted therapies for better outcomes in advanced cancer.

Talk with your doctor about immunotherapy as a possible kidney cancer treatment option. You’ll also want to ask about the risk for side effects and complications.