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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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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 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.
To learn more about how drugs that work on the immune system are used to treat cancer, see Cancer Immunotherapy.
To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.
The American Cancer Society medical and editorial content team
Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.
Atkins MB. UpToDate. Overview of the treatment of renal cell carcinoma; This topic last updated: Aug 26, 2019. Accessed at https://www.uptodate.com/contents/overview-of-the-treatment-of-renal-cell-carcinoma on November 22, 2019.
Correa AF, Lane BR, Rini BI, Uzzo RG. Ch 66 - Cancer of the kidney. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2019.
Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-2281.
McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial of high dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005;23:133-141.
McNamara MA, Zhang T, Harrison MR, George DJ. Ch 79 - Cancer of the kidney. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier: 2020.
Motzer RJ, Tannir NM, McDermott DF et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
National Cancer Institute. Physician Data Query (PDQ). Renal Cell Cancer Treatment – Health Professional Version. 2019. https://www.cancer.gov/types/kidney/hp/kidney-treatment -pdq. Updated September 6, 2019. Accessed on November 22, 2019.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer. V.2.2020. Accessed at: www.nccn.org on November 22, 2019.
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443-2454.
Last Revised: November 22, 2021
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