Immunotherapy treatment for melanoma

Melanoma is a type of skin cancer that is often mistaken for benign skin moles or beauty marks, but leaving it untreated can be dangerous, as it is the skin cancer with the highest mortality rate. One method to treat melanoma is immunotherapy, which ‘trains’ the immune system to recognise and destroy cancer cells. In this article, a consultant medical oncologist discusses how melanoma develops, and which types of immunotherapy are used to combat the cancer.

What is melanoma?

Melanoma develops when the cells that determine skin pigment, melanocytes, begin to behave abnormally. The primary reason for the abnormal behaviour stems from overexposure to ultraviolet radiation from the sun. It is most common in older people as they have spent more time under the sun, cumulatively, but anyone who spends a lot of time in the sun can develop it, especially if they have a lot of moles on their body or have had prior sunburn. It most commonly develops on the hands, face, neck, arms, and chest, as these areas of the body receive the most direct sunlight. Melanoma differs from regular moles due to the following signs:

asymmetry
ragged border
irregular or inconsistent in colour
a diameter larger than 6mm
changes in size, texture, shape or colour

This is known as the ABCDE rule (asymmetry, borders, colour, diameter, evolution).

In some cases, when the melanoma is caught early, the entire section of cancerous tissue can be surgically removed. But in more advanced cases, when the cancer cells may have spread beyond the localised area of the melanoma, then more intensive therapies need to be explored, like immunotherapy.

What is immunotherapy?

Immunotherapy, also known as a biological therapy, is a medical therapy that utilises the body’s own immune system to recognise and kill cancer cells through specialised drugs.

There are several types of immunotherapy. For treating melanoma, the most common approach is checkpoint inhibitor treatment. Checkpoint inhibitors use T-cells, which are white blood cells that circulate throughout the body within the blood to attack foreign or abnormal cells, though they are not always very effective against cancerous cells due to their own defences (proteins) that make them seem like normal cells to the immune system, thus evading detection due to the T-cells’ ‘checkpoint’ – the checkpoint being proteins on the T-cells that tell the cells to ignore normal cells (or at least those that appear so to the T-cells). With this type of immunotherapy, these checkpoints are surpassed, allowing the T-cells to be more aggressive and thorough.

This avenue of treatment is administered either by intravenous infusion or with several subcutaneous injections. Typically, immunotherapy treatment is conducted with several sessions, lasting weeks to months. Sometimes immunotherapy is used after skin cancer surgery as a way to ensure that any leftover cancer cells are dealt with.

Types of checkpoint inhibitors that are available for treating melanoma include:

PD-1 inhibitors
PD-L1 inhibitors
CTLA-4 inhibitors
CTLA-4 inhibitors
LAG-3 inhibitors

Not all checkpoint inhibitors will have the same administration and dosage, and their effects differ; the best course of therapy for the patient will be decided by their oncologist based on the extent and severity of their melanoma.

Another type of immunotherapy is tumour-infiltrating lymphocyte (TIL) therapy, where harvested T-cells invade cancerous tissue to shrink the melanoma mass. This involves removing one melanoma mass in surgery and ‘training’ and ‘multiplying’ the TILs before reintroducing them back into the patient’s body to seek and destroy melanoma cells.

TIL therapy is typically initiated with a short round of chemotherapy to prepare the body for the infusion.

Some other types of immunotherapy are:

Oncolytic virus therapy, where the patient is purposely administered with lab-altered viruses that are designed to infect and weaken cancer cells. One such treatment that is used for treating melanoma is talimogene laherparepvec (T-VEC). This is administered by injection directly into the melanoma.
Imiquimod cream, which is a topical drug that stimulates the immune system against cancer cells. It is used for very early-stage melanoma in sensitive or complex areas, mostly on the face. This can be abrasive to the skin and cause irritation.
Interleukin-2 (IL-2), which is a lab-synthesised version of interleukins, a naturally occurring protein in the cells that boosts the immune system, that is administered through intravenous infusions in addition to injections. It can shrink advanced melanomas in high doses, but this is often accompanied by intense side effects.

Are there side effects of immunotherapy for melanoma?

Immunotherapy can have significant side effects, which patients should consider before undergoing treatment. Possible side effects include:

Fatigue
Cough
Nausea
Skin rashes
Reduced appetite
Constipation or diarrhoea
Joint pain and stiffness

Some patients can experience a reaction from the administration of the drugs, much like an allergic reaction. This can include fever, chills, redness, swelling, itching, and dizziness. In more extreme instances, some patients may have severe autoimmune responses – as this therapy makes white blood cells more aggressive and removes their ‘checkpoints’, there is a possibility that they will begin to attack other parts of the body and organs, like the lungs, intestines, liver, hormone glands, or kidneys.

TIL therapy in particular is very intense on a patient’s body, and can have further, serious side effects like low blood cell counts, internal bleeding and infections.

Close and frequent communication between the patient and their cancer care team about how the patient is feeling and their symptoms is absolutely necessary in order to best evaluate the effectiveness and outcomes of immunotherapy. However, immunotherapy can be a powerful approach for dealing with advanced, inoperable, or treatment-resistant melanomas.