Immunotherapy for Melanoma: Advances in Predicting Treatment Response
Melanoma is a skin cancer and a difficult cancer to treat. Almost 100,000 people in the United States will be diagnosed with a new melanoma in 2019, and the number increases every year. The five-year relative survival rate, which means the number of people who are still alive five years after a melanoma diagnosis, is high if it’s detected early—as high as 98%. But if the cancer spread before it was diagnosed, the five-year relative survival rate drops to lower than 20%. However, with the advances of immunotherapy, these rates may improve.
Immunotherapy is a type of treatment that uses your own immune system to fight cancer. It is also called biologic therapy. Immunotherapy can work in one of three ways. It can:
Activate your immune system so it can effectively recognize and destroy the cancer cells
Stop the cancer cells from spreading throughout your body
Stop or slow the cancer cells from growing
Immunotherapy was first discovered as a way to treat cancer in the late 1800s, but it was not seriously studied until the mid-1900s. The U.S. Food and Drug Administration approved the first immunotherapy to treat cancer, kidney cancer in this case, in 1991. The first immunotherapy for melanoma was approved in 1998. Since then, researchers have been working to improve immunotherapy treatments and to discover new ones.
Immune checkpoint inhibitors called pembrolizumab and nivolumab boost your immune response to the melanoma cells. Another type of immunotherapy, using a CTLA-4 inhibitor called ipilimumab, also boosts the immune system, but using a different target.
Doctors use interleukin-2 less commonly today than in the earlier days of melanoma immunotherapy, usually if other immunotherapies haven’t worked. They use interleukin-2 to try and shrink tumors.
Virus therapy is another form of immunotherapy. T-VEC, for example, is a modified herpes simplex virus. When introduced into melanoma tumor cells, T-VEC destroys them. Researchers are also looking at vaccines. They have found that some patients respond well when vaccines like the BCG vaccine (for tuberculosis) are injected into the tumors.
These are just a few examples of the new and emerging treatments for melanoma.
Oncologists base their choice of immunotherapy for melanoma on what stage of disease you have and your individual medical history. Based on these and other factors, your oncologist will gauge how well you and your particular type of cancer might respond to immunotherapy. Even then, each patient responds differently and effectiveness isn’t guaranteed. Doctors determine success on whether the melanoma retreats or stops spreading, and on any side effects you may experience. Some patients can’t stay on a particular treatment plan, even if it appears to be working, because their side effects may be too severe.
As a result, oncologists need a way to determine if patients are likely to respond positively to immunotherapy, so they can minimize the risk of subjecting patients to a potentially difficult therapy with a low possibility of response against the cancer.
In 2018, researchers from the Center for Cancer Research at the National Cancer Institute developed a tool called IMPRES to help oncologists determine if a patient would respond well to an immune checkpoint inhibitor. The tool needs more study to determine its effectiveness, but one study that looked at nearly 300 samples was promising. According to researchers, they were able to correctly predict almost all of the patients who responded well to the treatment and almost half of those who did not.
Another study, published in early 2019, identified a biomarker that might be helpful in determining if patients will respond to a checkpoint inhibitor known as anti-PD1 therapy. The researchers had better success in determining if patients with a specific type of lung cancer would respond, but were less successful at predicting response for patients with melanoma. However, there was what they called “borderline significant” responses, which will inspire further research.
Researchers understand the importance of accurate treatment response predictions, so more studies are underway. A new study opened at the end of 2018 looking for measurable biomarkers in tumors in relation to treatment with nivolumab and ipilimumab. The researchers hope the findings in this study will help propel other research forward.
Melanoma is increasingly common, and while it is easier to address in the early stages, advanced melanoma is challenging to treat. With increasing availability of response predictors for immunotherapy, patients will have a better idea of which treatments will work for them, helping them to avoid treatments that may cause more harm than good.