How to Protect Yourself Against the Side Effects of Adjuvant Therapy for Melanoma
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 therapies. 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 recurrence. However, these therapies can cause severe, longterm and even life-threatening side effects. Anyone considering adjuvant therapy for melanoma should understand these potential side effects and their symptoms.
Different Adjuvant Therapies Have Different Risks
Melanoma patients who have been treated for stage 3 or stage 4 melanoma, but don’t show any signs of cancer, have two options for adjuvant therapy: Immune checkpoint inhibitors and targeted therapies. While immunotherapy and targeted therapies may have similar side effects, these reactions may vary in their severity as well as how they're treated, depending on the therapy, according to Douglas Johnson, M.D., assistant professor of medicine and Clinical Director, Melanoma Research Program, at Vanderbilt University Medical Center, Nashville, Tennessee. “These treatments can cause very different toxicities in the body,” he says.
Immune Checkpoint Inhibitors 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 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. They can hunt down cells that could otherwise metastasize, or spread. However, these drugs can also cause immune-related toxicities, overstimulating your immune system, 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
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 adjuvant therapies, but severe ones 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.
Checkpoint Inhibitors Side Effects Need Quick Treatment
Immune checkpoint inhibitors may 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 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.
- Encephalities or meningitis, or inflammation of the brain, causing fever and neurological symptoms such as confusion.
- Pneumitis , 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.
Reporting Side Effects Is Key to Preventing Serious Problems
Patients on checkpoint inhibitors should report all their symptoms, Dr. Johnson says. Even 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.
Targeted Therapy Has Fewer Severe Complications
Targeted therapies can be used on patients who have a gene mutation in their tumors known as BRAF. Targeted therapy medications target mutations that are driving the tumor's growth, Dr. McKean says. Most patients experience short-term side effects. These include fever, chills, fatigue, nausea, and rash and can be managed by pausing the drugs or giving steroids. “It’s very rare to have long-term complications from targeted therapy,” Dr. McKean says. Severe side effects are possible and could include cardiac toxicity, arrhythmias, or heart failure, but these generally aren’t seen in the adjuvant setting, according to Dr. McKean.
Long-term Side Effects Are Rare, But Can Happen
Although long-term side effects are rare, they’re more likely with immune checkpoint inhibitors than targeted therapy, Dr. McKean 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 medication for the rest of your life.” Other potential autoimmune complications include developing type 1 diabetes or adrenal insufficiencies. These too, would also require patients to take medications ongoing, Dr. McKean says.
Adjuvant Therapy Can Worsen Preexisting Autoimmune Conditions
Patients with preexisting autoimmune conditions should be aware that immune checkpoint inhibitors can, in rare cases, worsen their conditions. Patients with severe autoimmune conditions such as myathenia 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 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. Halting adjuvant therapy ahead of schedule doesn’t seem to affect outcomes, according to Dr. Johnson. “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” and they don’t need additional treatment, he says.