How to Protect Yourself Against the Rare—But Severe—Side Effects of Adjuvant Therapy for Melanoma

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For years, melanoma patients with a high risk of recurrence had few options for preventing cancer from returning.

But powerful new drugs are now available to completely remove cancer tumors. They're called adjuvant therapy.

Adjuvant therapy is an additional treatment given to some cancer patients after they’ve had surgery and other treatment. Its goal is to reduce the risk of the cancer recurring. However, the drugs used in these therapies can cause severe side effects, including the possibility of serious, long-term, and even life-threatening side effects. Though rare, these side effects are important to be aware of. Anyone considering undergoing adjuvant therapy for melanoma should understand and educate themselves about what these potential side effects and symptoms are. Read on to learn more.


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Different Adjuvant Therapies Have Different Concerns

Melanoma patients now have two options for adjuvant therapy: immune checkpoint inhibitors and targeted therapies. The Food and Drug Administration has approved the use of these therapies for patients who have been treated for stage 3 or stage 4 melanoma, but don’t show any signs of cancer.

Patients should be aware that while immunotherapy and targeted therapies may have similar side effects, these reactions may be treated differently depending on the therapy you’re receiving, according to Douglas Johnson, M.D., assistant professor of medicine and Clinical Director, Melanoma Research Program, at Vanderbilt University Medical Center, Nashville, Tennessee.

Also, some symptoms may be more concerning and have the potential to become severe, depending on your treatment, Dr. Johnson says.

“How a doctor treats a side effect may be really different, depending on which adjuvant therapy you are getting,” he says. “These treatments can cause very different toxicities in the body.”


Immune Checkpoint Inhibitors: They Excite Your Immune System

Immune checkpoint inhibitors are immunotherapy drugs that work by over-activating your immune system. When employed as an adjuvant therapy, these drugs use your own immune system to attack microscopic amounts of melanoma cells that may be hiding out in your body even after you’ve undergone surgery and treatment for cancer, says Meredith McKean, M.D., a research faculty member at Sarah Cannon Research Institute at Tennessee Oncology, Nashville, Tennessee.

Immune checkpoint inhibitors can be an effective way of hunting down these remaining melanoma cells that could otherwise metastasize, or spread, to other parts of the body.

However, these drugs can also cause immune-related toxicities, where your immune system is overly stimulated, causing inflammation and other adverse effects to your organs and your body’s systems and functions, Dr. McKean says.


Side Effects of Immune Checkpoint Inhibitors

These immune-related side effects can affect any organ or tissue in the body, causing a variety of symptoms. Most patients experience some side effects while undergoing one of these adjuvant therapies, but severe side effects are typically rare, says Dr. McKean.

The most common, less severe, side effects include fatigue, cough, nausea, itching, skin rash, decreased appetite, constipation, joint pain, and diarrhea.

“Up to 90% of patients who use checkpoint inhibitors in the adjuvant setting will have some side effects from immune checkpoint inhibitors,” Dr. McKean says.


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Severe Side Effects of Immune Checkpoint Inhibitors that Need to be Treated Quickly

Immune checkpoint inhibitors DO have the potential to cause severe side effects when used in the adjuvant setting (though, as Dr. McKean mentioned, the more severe ones tend to be rare). But better to be safe than sorry and know what these side effects are. They include:

  • Myocarditis, or inflammation of the heart, which includes symptoms such as chest pain, shortness of breath, and fatigue.
  • Encephalitis or meningitis, or inflammation of the brain, causing fever and neurological symptoms such as confusion.
  • Pneumonitis, or inflammation of the lungs, which can cause shortness of breath.
  • Colitis, or inflammation of the colon, which can cause life-threatening diarrhea or even perforation of the colon.


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Reporting Side Effects is Key to Preventing Serious Problems

The potential for severe side effects with immune checkpoint inhibitors is why patients should report all of their symptoms to health care providers, Dr. Johnson says. Even vague symptoms, such as severe fatigue and mild chest pain, can be an indication of more severe side effects, such as myocarditis or pneumonitis.

“A major cause of fatal side effects are due to either physicians not recognizing the side effects or patients not reporting the side effects, which lead to long delays in treatment,” he says. “But there is also a subset of side effects like myocarditis which, if not treated rapidly, could be fatal.”

While Dr. Johnson says that less than 1% of patients treated with checkpoint inhibitors for adjuvant therapy have died, fatalities have happened.


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Targeted Therapy Tends to Have Fewer Severe Complications

Targeted therapies can be used on patients who have a specific gene mutation in their melanoma tumors known as the BRAF mutation. Targeted therapy medications are designed to target specific mutations that are driving the growth and spread of the tumor, Dr. McKean says.

Most patients experience short-term side effects from targeted therapy. Common side effects include fever, chills, fatigue, nausea, and rash. These can usually be managed either by temporarily stopping the drugs or giving steroids. Once side effects are under control, most patients can resume targeted therapy.

“It’s very rare to have any long-term complications from targeted therapy,” Dr. McKean says. “Overall, it’s a fairly safe regimen.”

Severe side effects from targeted therapy are possible and could include cardiac toxicity, arrhythmias, or heart failure, but these side effects generally aren’t seen in the adjuvant setting, according to Dr. McKean.


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Long-term Side Effects Are Rare, But Can Occur

Although long-term side effects are rare, they’re more likely with immune checkpoint inhibitors than targeted therapy, Dr. McKean says. In those cases, people experience long-term side effects, some of which may stay with them for the rest of their lives, she says. These can include life-long autoimmune disorders.

“One of the common places for the immune system to become overactive and start attacking itself is the thyroid gland,” she notes.

“If while on adjuvant therapy, your body makes antibodies that start attacking your thyroid, you may need thyroid replacement mediation for the rest of your life.”

Other potential autoimmune complications include developing type 1 diabetes or adrenal insufficiencies. These would also require patients to take medications for the rest of their lives, Dr. McKean says.


In severe cases of guillain-barré, people can become temporarily paralyzed.
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Adjuvant Therapy Can Worsen Preexisting Autoimmune Conditions

Patients with preexisting autoimmune conditions should be aware that immune checkpoint inhibitors can, in rare cases, cause their conditions to worsen.

Having an autoimmune condition doesn’t necessarily prevent patients from receiving checkpoint inhibitors for adjuvant therapy, and many of these patients can be well supported through the therapy, Dr. McKean says.

But patients with severe autoimmune conditions such as myasthenia gravis, guillain-barré, or lupus should have a thorough discussion with their oncologist about their symptoms and how well their condition is controlled before beginning immune checkpoint inhibitors for adjuvant therapy.

“There is a risk those symptoms could get worse,” Dr. McKean says. “It’s very rare to develop a toxicity, even for patients with an autoimmune condition. But it can be devastating when it does.”


If Side Effects Become an Issue, Adjuvant Therapy Might be Stopped

Adjuvant therapy is currently given to patients for about a year after the initial surgery and treatment for melanoma. But if you show symptoms of severe side effects that aren’t controlled, your doctor may decide to stop adjuvant treatment early, Dr. McKean says.

Studies have shown about a 10% chance of having a toxicity that would require a patient to stop immune checkpoint inhibitors early in the adjuvant setting, she says.


Stopping Adjuvant Therapy Early May Not Impact Your Outcome

If you do have to stop therapy early, know that it’s the safest and best choice for you, Dr. Johnson says. If you’ve had a serious side effect, continuing treatment could be dangerous.

Stopping adjuvant therapy ahead of schedule doesn’t seem to affect outcomes, according to Dr. Johnson. Those who’ve had to stop therapy earlier don’t seem to have poorer outcomes than those patients who completed a full year of adjuvant therapy, he says.

“Patients who have to stop early from side effects seem to do just as well as patients who don’t,” Dr. Johnson notes.

After patients have undergone a certain amount of adjuvant treatment, their immune systems seem to be appropriately “turned on” by the therapy and they don’t need additional treatment, he says.