Renal cell carcinoma (RCC) is a type of kidney cancer that originates in the tubules of the kidney. Immunotherapy has emerged as a significant treatment option for RCC. It works by harnessing the body’s own immune system to identify and fight cancer cells. This approach offers new avenues for managing the disease.
What Immunotherapy Is
Immunotherapy represents a distinct approach to cancer treatment, unlike chemotherapy or radiation, which directly attack cancer cells. Instead, it focuses on activating the body’s natural defenses, the immune system, to recognize and destroy cancer cells. The immune system normally identifies and eliminates abnormal cells, but cancer cells often develop ways to evade this detection, such as by expressing proteins that turn off immune cells.
Immunotherapy drugs work by disrupting these evasion mechanisms, essentially “releasing the brakes” on the immune system. This allows immune cells, particularly T cells, to respond more strongly and effectively attack the cancer. This aims to achieve a more sustained anti-tumor response.
Key Immunotherapy Approaches for RCC
The primary class of immunotherapy drugs used for renal cell carcinoma are immune checkpoint inhibitors. These drugs target specific proteins, such as PD-1 (programmed cell death protein 1), PD-L1 (programmed death-ligand 1), and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), which act as “checkpoints” to regulate the immune response. Cancer cells can exploit these checkpoints to hide from the immune system, but checkpoint inhibitors block this interaction, allowing the immune cells to attack the tumor. Examples of these inhibitors used in RCC include nivolumab, pembrolizumab, ipilimumab, avelumab, and atezolizumab.
Historically, cytokines like interleukin-2 (IL-2) and interferon-alpha (IFN-α) were used to treat RCC by stimulating immune cells. While they showed some clinical activity, their use is now less common due to significant toxicities and lower overall response rates compared to newer therapies. High-dose IL-2, for instance, could induce complete responses in a small percentage of patients, but its severe side effects limited its broader application.
Current treatment strategies increasingly involve combination therapies, often pairing different immunotherapy drugs or combining immunotherapy with targeted therapies. For instance, combining a PD-1/PD-L1 inhibitor with a CTLA-4 inhibitor, such as nivolumab and ipilimumab, can lead to improved overall survival and response rates for advanced RCC. Combinations of immune checkpoint inhibitors with targeted therapies, like axitinib with pembrolizumab or avelumab, or cabozantinib with nivolumab or atezolizumab, are also common, aiming for greater effectiveness by disrupting pathways that support tumor growth and blood supply.
When Immunotherapy is Used and Treatment Experience
Immunotherapy is primarily used for advanced or metastatic renal cell carcinoma. It can be a first-line treatment or used after other therapies have been tried. Immunotherapy is also gaining a role in earlier stages, specifically as adjuvant therapy after surgery in patients with a high risk of cancer recurrence. For example, pembrolizumab has been approved as an adjuvant treatment after surgery to help reduce the risk of recurrence.
Immunotherapy drugs are typically administered intravenously, meaning they are given through a drip into a vein. The frequency of treatment varies depending on the specific drug or combination, but it often involves infusions every few weeks. The duration of treatment can range from several months to over a year.
During treatment, patient response is closely monitored through various methods. This includes regular medical imaging like CT scans to assess tumor size changes, and blood tests to check for overall health markers and potential side effects. Adapted criteria, such as immune RECIST (iRECIST), are sometimes used for follow-up assessments to better account for atypical response patterns seen with immunotherapy, where tumors might initially appear to grow before shrinking.
Navigating Treatment Side Effects
Immunotherapy for renal cell carcinoma can cause side effects, often referred to as “immune-related adverse events” (irAEs). These occur because the activated immune system, while targeting cancer cells, can also affect healthy tissues and organs. The specific side effects can vary depending on the immunotherapy drug or combination used.
Common irAEs include:
Fatigue
Skin rashes
Diarrhea
Inflammation of hormone-producing glands, such as thyroid issues (hypothyroidism or hyperthyroidism)
Inflammation in organs like the lungs (pneumonitis), liver (hepatitis), and kidneys (nephritis, which can manifest as proteinuria)
Heart issues (myocarditis)
Nervous system issues
Management of these side effects is a collaboration between the patient and their healthcare team. Prompt reporting of any new or worsening symptoms is important. For mild to moderate irAEs, treatment may involve symptom management, while more severe reactions often require the use of corticosteroids to suppress the overactive immune response. The dose and duration of corticosteroids are carefully managed. In some cases, if side effects do not improve with corticosteroids, other immunosuppressive therapies may be considered, and treatment with immunotherapy might be paused or permanently discontinued.
Outlook for Patients with RCC
Immunotherapy has significantly changed the outlook for patients with renal cell carcinoma, improving outcomes for many individuals. This is particularly true for those with advanced or metastatic disease, where immunotherapy, especially in combination with targeted therapies, has been shown to prolong overall survival and progression-free survival compared to traditional treatments. For the first time in decades, adjuvant immunotherapy after surgery has also demonstrated an overall survival benefit for certain high-risk patients, delaying recurrence and extending lives.
Ongoing research continues to explore new combinations and therapeutic strategies to enhance the effectiveness of immunotherapy for RCC. Efforts include investigating novel immune checkpoint targets, as well as exploring personalized cancer vaccines and cellular therapies. These advancements offer continued hope for developing more effective and potentially curative treatments for patients with RCC.