What Patients Should Know About a Melanoma Diagnosis

Melanoma care varies by stage: © stock.adobe.com.

Melanoma treatment depends on stage. Early-stage cases may need only surgery, while deeper tumors might require lymph node evaluation and additional therapy, according to Dr. Douglas Johnson, who went on to say that immune therapies help the body attack cancer, while targeted therapies are given to patients with BRAF mutations to block cancer growth. 

Johnson is a physician-scientist and professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee, where he leads the melanoma clinical research program.

CURE sat down with Johnson for a “Q&A” to discuss how treatment decisions are made, what to expect with immune therapy, and where research is headed next.

CURE: For patients newly diagnosed with melanoma, what are the most important things to know about the disease and its treatment options today?

Johnson: Well, it certainly depends on a number of factors, and the staging of the melanoma is really important to consider because that significantly affects the next steps for patients. Usually, a biopsy is performed, and that's how a patient would learn they might have melanoma. So, it really depends on the depth of the melanoma. That's probably the first consideration when figuring out the next steps and whether the melanoma has what's called an ulceration on its surface. These factors would potentially determine the subsequent course of action.

If a patient has a very early-stage melanoma, defined as less than 0.75 or less than 1 millimeter in depth, then they would typically only require surgery, usually a wide local excision, and that would be it. This might be managed with surgery alone or in collaboration with dermatology. If the melanoma is a bit deeper, then they would definitely need to see a surgeon and understand whether there is any lymph node involvement, potentially requiring a more extensive operation. Depending on the findings during those operations, we would then need to consider any additional treatment afterward.

Can you explain what immune and targeted therapies are? How have they changed the way we treat melanoma?

For patients with very early-stage melanoma, surgery alone is typically all that's needed. However, for patients whose melanoma is either very deep and has high-risk factors, has spread to the lymph nodes, or has even spread to other organs, we use other kinds of treatments. This is because we know that, generally speaking, the higher the risk of melanoma or the more it has spread, something like surgery by itself may not be curative.

In those situations, we consider treatments like immunotherapies and targeted therapies. Immunotherapies are treatments given intravenously, similar to chemotherapy, that boost the immune system to attack the cancer. They achieve this in different ways, but the most common type of immunotherapy is called anti-PD-1 treatment. These treatments essentially boost T cells, which are attack cells in the immune system, to go after the melanoma and eliminate it.

Targeted therapies work quite differently. About half of melanomas have a specific gene mutation in a gene called BRAF. This gene mutation is present only in the tumor and not in the rest of the body. However, there are pills that can be given that specifically target that BRAF mutation. This mutation sort of functions like an "on switch" for the cancer, so by blocking that on switch, we can hopefully stop the cancer cell growth and division and cause the cancer to shrink.

How do biomarkers help determine which melanoma treatments might work best for patients? So

We have good biomarkers for targeted therapy. For example, if the cancer has a BRAF mutation, then that person will potentially respond to BRAF and MEK inhibitor treatments. MEK is the next link in the chain for targeted therapy, and we usually use those treatments together.

Unfortunately, we don't really have that for immunotherapy yet. There are a couple of markers that are somewhat experimental, but nothing that has really reached prime time. So, at this point, unfortunately, with immunotherapy, we kind of have to just administer it and see what happens, rather than having a great biomarker or test that can tell us ahead of time whether the patient is likely to respond or not. That is certainly a limitation of our current science.

Are there specific risk factors that might make some patients more likely to experience side effects from immune therapy?

Immune therapies cause side effects by activating the immune system. Of course, we like that when it attacks the tumor, but we don't like it so much when it attacks the rest of the body. We so far have gotten really good at describing the kinds of side effects that immune therapies might cause. We know very well as far as the percentages of how many patients are going to or have experienced different kinds of side effects. We're really not very good at identifying an individual patient either which side effect or whether they're going to have a side effect at all.

There's a couple of factors that seem to correspond a bit to whether a patient will have side effects. One obvious one is that if a patient receives combination immune therapy, they're more likely to have a side effect. So, block the immune system in multiple ways, or if we block the brakes on the immune system and boost the immune system in multiple ways, and those patients are more likely to have a side effect. So for example, in patients who are getting a combination of two immune therapy drugs called Yervoy and Opdivo or ipilimumab and nivolumab, about half of those patients will have a severe immune system reaction, compared to if patients who are just getting one of those drugs — just the anti PD-1 drug nivolumab — they're only about 15% as likely to get a side effect.

Combination is another one is that's another weak side effect or patients that already have a history of autoimmune disease. If somebody's immune systems already dysregulated, then they're more likely to get an immune side effect from treatment. Surprisingly, it's certainly not by any means 100%.

A lot of patients, even with autoimmune problems, can tolerate treatment very well. And other than that, we don't really have there's a lot of research ongoing to try to figure out genetic factors or other potential tests that would tell us who's going to have side effects and who's not. However, we're still just starting to understand that.

What are you currently learning about treating patients with melanoma who also have other health challenges like autoimmune disease or kidney problems?

So, immunotherapies, in general, are much better tolerated than some of our traditional cancer treatments, like chemotherapy. We are able to treat a broader range of patients than we used to be able to with conventional chemotherapy combinations. There are actually very few absolute contraindications, meaning very few things that would completely prevent a patient from receiving immunotherapy. However, a few factors that I consider that may make treatment more challenging would be significantly impaired functional status. By that, I mean people who have great difficulty even getting up and around and performing their normal daily activities. We know that even something like immunotherapy can be very hard on those patients, and they are also very unlikely to benefit.

Patients with very severe autoimmune diseases can be very challenging, but the vast majority of patients with autoimmune diseases can actually still receive treatment. Often, we will co-manage that patient with their rheumatologist, neurologist, or whichever doctor is taking care of their autoimmune disease. We may have to tweak some of their regimen a little bit and treat them with other treatments that sort of block the immune system a bit and then tamp it down just a tiny bit.

Generally speaking, patients with heart problems, lung problems, or kidney problems can generally receive immunotherapy. We just have to monitor them a bit more closely. I will say the one other area that is a bit concerning and certainly an area of research is treating patients who have had organ transplants. If someone has had a liver transplant or a kidney transplant, those patients are at risk of rejecting their organ. Some new studies have recently suggested ways they might be able to be treated with pulses of steroids and things like that, and they can do okay, it seems like, but that is certainly an area that we are just starting to understand.

Are there any developments that seem to be improving melanoma outcomes in the near future?

One amazing thing about melanoma is that it tends to be the cancer where new immunotherapies are first proven, studied, and understood. For example, basically all three classes of immune checkpoint inhibitors, or immunotherapies, were first studied in melanoma, and all the combinations were first studied in melanoma. There are also new types of treatment called oncolytic viruses, which are basically viruses that treat the cancer. We actually have one of those already available in melanoma, and it looks like more active ones are coming.

There are also some cancer vaccines being studied in melanoma, including a study well on its way to finishing that aims to prevent melanoma from recurring. That is also quite exciting. And then finally, there is a class of treatment called tumor-infiltrating lymphocytes, or TILs, where a tumor is taken out, the white blood cells are harvested from the tumor, they are supercharged, and then given back to the patient.

This was also something that was just approved in melanoma about a year ago, and there are next-generation products coming that have fewer side effects and may be more active as well. So really, I think melanoma continues to be on the cutting edge of the immunotherapy revolution, not simply with immune checkpoint inhibitors, but also with a lot of other innovative ways of harnessing the immune system against cancer.

What should patients and families keep in mind during Melanoma Awareness Month when it comes to prevention or early detection?

I think certainly you know, keeping in mind that ABCDEs, which are basically looking at patient’s moles, that those, of course, stand for asymmetry (A), border (B), color (C), diameter (D) and evolution (E). So basically, if a mole is very regular, if it's changing color, if it's an unusual color, if it's if it's growing — that would be a reason to get to get checked out.

Certainly, catching melanoma early is very good in terms of preventing melanoma recurrences, and so having regular checkups of dermatology for patients who have had a history of skin cancer or other skin problems can also be very helpful. But catching it early is really important. And I guess the other good thing is that we're always making progress with melanoma, and so hopefully, even for people that do have more aggressive or later stage melanoma, we do have a lot of new treatment options and active treatments.

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