Immunotherapy for melanoma has been gaining traction among doctors in the recent years and has worked well to a great extent especially in advanced melanoma. Melanoma is a type of metastatic skin cancer that develops from melanocytes, cells responsible for producing pigmentation protein (melanin) in your body.
As with many other human cancers the true cause of melanoma remains idiopathic (unknown). However, there are several risk factors that have been implicated after being found to correlate with the occurrence. One such risk for melanoma is prolonged exposure to sunlight.
Types of Melanomas
There are two types of melanomas: superficial spreading melanoma and nodular melanoma. We shall highlight a few details about these types of Melanomas before we embark on immunotherapy.
Superficial Spreading Melanoma
This type of skin cancer is the most common and accounts for about 70% of all skin cancers. As with other types of skin cancers, spending a lot of time under direct sunlight is a major risk factor for superficial melanoma.
Superficial spreading melanoma occurs when malignant melanocytes migrate along the epidermis, causing a slow-growing tumor that spreads outwards from the original spot. After some time, this type of cancer can spread into deeper layers of the skin.
Nodular Melanoma
Nodular melanoma is a rapidly growing tumor that forms small lumps under the skin. This type of melanoma is the most aggressive in destroying the skin and grows more in thickness compared to its increase in diameter.
Both types of melanomas have a high risk of metastasis (spreading). They both do not respond well to primary options of cancer treatment and that is where the option of immunotherapy would come in handy.
Use of Immunotherapy for Melanoma Treatment
Immunotherapy is a treatment that uses the immune system to fight disease. In immunotherapy, the patient’s own immune system is stimulated to attack cancer cells.
Immunotherapy drugs work by either boosting the patient’s natural defenses or blocking the signals sent by tumors to suppress the immune system.
For instance, immune checkpoint inhibitors block the signaling pathways that normally prevent T cells from attacking normal cells. By doing so, they allow the immune system to recognize and destroy abnormal cancer cells.
Immunotherapies are given intravenously. These treatments may cause side effects such as fatigue, fever, chills, nausea, diarrhea, vomiting, mouth sores, cough, shortness of breath, weight loss, and pain at injection site.
Immunotherapy for Melanoma FDA-approved Immune Products
There are FDA approved immune products for the treatment of melanoma. These products include ipilimumab (Bristol-Myers Squibb), pembrolizumab (Keytruda; Merck & Co.), nivolumab (Opdivo; Bristol-Myers Squib), and durvalumab (Imfinzi; AstraZeneca) for advanced melanoma.
There are many other products that are under development while others are in early stages of research. Let’s discuss the few examples some of which we listed above including explaining their mechanisms of action here:
1. Ipilimumab (Bristol-Myers Squibb)
Ipilimumab was first approved for the treatment of melanoma in 2011. This product works by blocking CTLA-4, a protein that helps regulate the activity of T cells.
Since CTLA-4 downregulates the immune responses, blocking this protein unlocks the full potential of your T cells to fight melanoma. Better prognosis has been reported with this product so far.
2. Pembrolizumab and nivolumab
Pembrolizumab and nivolumab were both approved in 2014. They work by blocking PD-1, a protein that stops T cells from killing cancer cells. The blockade of PD-1 signal will hence disable apoptosis in T cell immune responses.
Blocking this protein therefore ensures that there is no unnecessary apoptosis at a time when the T cells are most needed. This immunomodulation will eventually lead to enhancement of melanoma-specific T cell responses and give better outcomes.
3. Atezolizumab
This drug is a monoclonal antibody raised against PD-L1 a protein over-expressed by melanoma tumor cells but also expressed by some normal immune cells in low amounts.
Blocking PD-L1 has proven very helpful in adaptive immune responses against melanoma. This drug can be combined with vemurafenib in mutant melanoma and work very well.
It is the treatment of choice in stage 4 melanoma where surgery is not an option because of the advanced metastasis of the disease.
4. Durvalumab
This is another monoclonal antibody which was approved for treatment of melanoma in 2017. It works by blocking PD-L1, a protein that suppresses T cell responses.
A blockade of this protein in patients with melanoma ensures that the T cells that are specific for melanoma antigens can proliferate unrestricted and hence control the spread of the disease.
5. Relatlimab
This is a monoclonal antibody that target to block lymphocyte activation gene-3 (LAG-3). LAG-3 is a checkpoint receptor protein and so blocking it helps in amplifying cancer-specific T cell responses against melanoma.
Relatlimab is mostly given in combination with a PD-1 inhibitor called nivolumab. This combination drugs work synergistically and are helpful particularly where surgery can’t work.
Side Effects of Immunotherapeutic Treatment for Melanoma
Like many other drugs in the treatment of cancer, immunotherapeutic products have some effects. There is therefore the need for your doctor to weigh between the expected benefits and the side effects that you are likely to suffer.
As highlighted earlier, some common side effects that have been reported include Anorexia, dizziness, breathlessness, fever, occasional chills, fatigue, skin irritation, diarrhea, wheezing, rashes, and constipation. There may be other rare side effects that vary from patient to patient.
Research on Immunotherapy for Melanoma
While research for the discovery of new immunotherapeutic products continues, interventional clinical trials continue to show the clinical value of the already discovered products.
For instance, a study published in 2015 showed that patients who received ipilimumab had longer survival than those who did not receive it.
Another study published in 2016 showed that patients who received pembrolizumabb had longer survival than those treated with chemotherapy alone.
In this case the patients who received immunotherapy lived an average of 10 months after diagnosis compared to 5.1 months for those who did not receive immunotherapy.
Advice on the Use of Immunotherapy for Melanoma Treatment
The National Comprehensive Cancer Network recommends using immunotherapy for patients with stage III or IV melanoma who have no brain metastases.
Further, immunotherapy should only be used where other primary interventional cancer therapies have failed.
Immunotherapy can be combined with radiation therapy. The two types of treatments for melanoma will work synergistically.
Radiation therapy kills some cancer cells while leaving others intact. However, when combined with immunotherapy, the remaining cancer cells are killed by the immune system.
In addition, immunotherapy can be used in combination with targeted therapy. Targeted therapy targets specific molecules that help cancer cells grow and spread. The idea here is to stop the metastasis.
Immunotherapy can be given before, during, or after surgery. Surgery removes the primary tumor and any nearby lymph nodes.
If the cancer has spread to these lymph nodes, then the surgical procedure can help remove them too. Thereafter, immunotherapy can be administered via pill, shot, or infusion to help further reduce the cancerous cells.
Conclusion
Immunotherapy works by enhancing the patient’s immune system to work smarter to prevent the metastasis of melanoma.
Immunotherapy is a perfect alternative especially where primary cancer treatment options like surgery, chemotherapy and radiotherapy have failed.
Immunotherapy has proven to be of value in advanced melanoma especially in stage III and stage IV. It shows demonstrated the ability to significantly improve the disease prognosis.
