Immunotherapy represents a development in the treatment of advanced melanoma, harnessing the body’s own immune system to combat cancer. This approach uses medicines to help a person’s immune system more effectively identify and eliminate cancerous cells. Unlike traditional treatments that directly target the cancer, immunotherapy empowers the body’s natural defenses. These therapies have changed the outlook for individuals with melanoma that has spread or cannot be removed by surgery.
Before the availability of immunotherapy, the average life expectancy for patients with metastatic melanoma was approximately nine months. Today, these treatments have substantially improved survival rates. The core principle is to overcome the methods that cancer cells use to evade detection by the immune system. This allows the body’s defense mechanisms to function as intended, recognizing and fighting the malignant cells.
How Immunotherapy Works Against Melanoma
The human immune system has a complex network of checks and balances to prevent it from attacking the body’s own healthy cells. A part of this system involves proteins on immune cells called “checkpoints,” which act like switches that can be turned on or off to start an immune response. Melanoma cells can exploit these safeguards by displaying proteins on their surface that tell the immune system’s T-cells to stand down. This interaction allows the cancer to grow unchecked by using these checkpoint pathways to avoid being destroyed.
Immunotherapy drugs, specifically a class known as checkpoint inhibitors, are designed to disrupt this process. These drugs are monoclonal antibodies that block checkpoint proteins, such as CTLA-4, PD-1, and PD-L1. By blocking these proteins, the drugs “release the brakes” on the immune system. This action prevents the melanoma cells from deactivating the T-cells, allowing the immune cells to recognize the cancer as a foreign threat and mount an attack.
This reawakened immune response is systemic, meaning the T-cells can then travel throughout the body to find and destroy melanoma cells wherever they may be. The effects can be long-lasting, as the immune system may develop a “memory” of the cancer cells. This ability to create a durable response is a primary feature of immunotherapy.
Types of Immunotherapy Drugs Used
A variety of immunotherapy drugs are approved for treating melanoma, categorized by the specific checkpoint protein they target. Each class functions in a slightly different way to interrupt the signals that allow cancer cells to evade the immune system.
PD-1 Inhibitors
Pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs that target PD-1, a checkpoint protein found on the surface of T-cells. By blocking PD-1, these inhibitors prevent melanoma cells from deactivating the T-cells, thereby boosting the immune response against the cancer. These drugs are used for melanomas that have spread or cannot be surgically removed and can also be given after surgery to reduce the risk of the cancer returning.
CTLA-4 Inhibitors
Ipilimumab (Yervoy) is a medication that blocks CTLA-4, another protein on T-cells that works to suppress immune responses. By inhibiting CTLA-4, ipilimumab helps to keep the T-cells in an active state, allowing them to fight melanoma cells more effectively. This was one of the first checkpoint inhibitors to show a survival benefit for patients with advanced melanoma.
Combination Therapy
For a more robust immune response, doctors may prescribe a combination of a PD-1 inhibitor and a CTLA-4 inhibitor, such as nivolumab plus ipilimumab. Blocking two different checkpoint pathways simultaneously can be more effective than blocking just one. Studies have shown that this approach can lead to better survival rates compared to using a single drug alone.
Oncolytic Virus Therapy
Talimogene laherparepvec (T-VEC), also known as Imlygic, is a different kind of immunotherapy. It involves a modified herpes virus that is injected directly into melanoma tumors. The virus is engineered to replicate inside cancer cells, causing them to rupture and die. This process releases substances that stimulate the immune system to recognize and attack melanoma cells elsewhere in the body.
The Treatment Process
Immunotherapy for melanoma is administered in a clinical setting. Most of these therapies, particularly checkpoint inhibitors, are given intravenously (IV), and patients receive this treatment as an outpatient, allowing them to go home the same day. An infusion session lasts between 30 and 90 minutes, though the overall appointment can take longer to account for pre-treatment checks.
The frequency of infusions varies depending on the specific drug or combination of drugs being used. A treatment cycle could be scheduled every two, three, four, or six weeks. The duration of the treatment course is determined by how the melanoma responds and how well the patient tolerates any side effects. For advanced melanoma, treatment may continue as long as it remains effective and the side effects are manageable.
Potential Side Effects and Management
Because immunotherapy works by activating the immune system, it can cause the body’s defenses to attack healthy cells and organs. These resulting side effects are known as immune-related adverse events. While many people experience mild to moderate side effects, they can sometimes be more serious, so patients must report any new or worsening symptoms to their healthcare team immediately.
Common side effects often involve the skin, presenting as rashes or itching. The gastrointestinal system can also be affected, leading to diarrhea, which is a sign of inflammation in the colon known as colitis. Another frequent side effect is fatigue, a persistent feeling of tiredness that may continue even after treatment ends.
Inflammation can also occur in other parts of the body. The endocrine glands, such as the thyroid or pituitary, can become inflamed, leading to hormonal imbalances. In some cases, the lungs may be affected, causing a cough or shortness of breath, a condition called pneumonitis.
The management of these side effects is a standard part of the treatment process. For mild reactions, topical creams or simple medications may be sufficient. If side effects become more severe, they are often managed with other drugs, such as corticosteroids, which work by suppressing the overactive immune response. Prompt communication with the medical team ensures that these issues can be addressed quickly and effectively.