Side Effects

Although using immunotherapy to treat melanoma typically results in fewer side effects that are less severe than those associated with other forms of cancer treatment, some side effects still can occur, and some can be severe.

However, data on the long-term effects of immunotherapy are not yet available. Not everyone will experience the same side effects with immunotherapy, and some people may not experience any side effects at all. Symptoms can vary in severity and differ according to the type of immunotherapy (see Table 1).

Many side effects can be managed with over-the-counter medications. However, some symptoms can be severe.

With immunotherapy, side effects can indicate that the immune system has become too active and could put patients at risk for an autoimmune disorder. If treated early, these symptoms can be corrected with corticosteroids, and immunotherapy can be resumed at a later date.

Often, the dose of the immunotherapy medication can be adjusted to prevent future autoimmunity, if caught in time. It is important to educate the patient about what they should do if they have symptoms. Emphasize to them the importance of contacting a member of your health care team immediately and frequently so you can help monitor them and their symptoms. Remind them to seek treatment immediately for any medical emergencies, including high fever, severe abdominal pain or shortness of breath.

Common side effects associated with immunotherapy include the following.

Immune-mediated Adverse Reactions

Immune-mediated adverse reactions have not been a commonly reported side effect of immunotherapy, but they can occur with certain types of immunotherapy medications. Explain to your patient how to recognize an immune-mediated adverse reaction, as some of these side effects may not produce symptoms they can feel. These reactions occur when the immune system is overstimulated by the treatment and may cause inflammation, including swelling, redness or pain, that they may or may not be able to physically feel.

With immune-mediated adverse reactions, certain organs may become inflamed, which can cause hepatitis (liver), dermatitis (skin) and enterocolitis (small intestine, colon). It can also damage the nerves and endocrine glands. One of the more common side effects with checkpoint inhibitors and cytokines is a change in the function of the thyroid gland. This can sometimes be corrected with thyroid replacement medication and requires monitoring of thyroid function on a regular basis.

If not treated early, these symptoms can lead to life-threatening complications. Treatment will need to be sought early for immune-mediated adverse events.


Fatigue is the most common side effect reported in multiple immunotherapies. Fatigue and feeling tired are often found in the class of therapies known as checkpoint inhibitors, cytokines and oncolytic virus therapy.

The fatigue associated with cancer is different than simply feeling tired because they haven’t had enough rest. Fatigue from cancer or its treatment may cause people to feel physically, emotionally or mentally tired and exhausted. Explain that symptoms of fatigue include missing work, spending less time with friends and family, sleeping more, and having difficulty remembering things or not thinking clearly. Encourage them to talk with you about any of these symptoms. 

An evaluation of the patient’s fatigue level throughout their treatment and recovery, including doing a distress screening, is recommended.


Flu-like Symptoms

Flu-like symptoms, such as fever, chills, aches, headache, drowsiness, nausea, vomiting, loss of appetite and low blood cell counts, can occur if treatment includes cytokines or oncolytic virus therapy. These symptoms can range from mild to severe.

To manage flu-like symptoms, getting enough rest will be important. You might recommend taking acetaminophen. You also might suggest taking any oral treatments at bedtime to help minimize symptoms. If a cough develops, suggest they drink plenty of water and other fluids to keep their throat moist.


Diarrhea is a common side effect with the checkpoint inhibitor class of immunotherapies for melanoma, specifically the PD-1 and CTLA-4 inhibitors.

The symptoms can vary in severity and duration. It is important to discuss what to expect with this side effect, including how long it may last and when to consider emergency treatment. Diarrhea can lead to severe dehydration and electrolyte imbalance but also could be a symptom that the immune system is going into overdrive.

Tips to manage diarrhea include drinking clear liquids, avoiding milk products, eating low-fiber foods, eating frequent small meals, choosing foods that are high in potassium, avoiding foods that can irritate the digestive tract and trying probiotics. Anti diarrheals may be useful for minimal diarrhea but corticosteroids should be started if more than seven bowel movements per day occur, or if diarrhea is associated with crampy abdominal pain or hemorrhage.

Remind patients to call your health care team if they experience symptoms that interfere with their daily activities, such as severe abdominal cramping, or that cause them to fear leaving their home.

Mild Skin Reactions

Mild skin reactions, such as bumpy or itchy red rashes, can occur. Checkpoint inhibitors most often feature itching and/or rashes as common side effects.

Other skin problems include yellowing or other changes in skin color, blistering, hives, pale patches and flushing or redness.

Although these symptoms are rarely severe, they can be very uncomfortable. Depending on the type of itching, you might recommend a corticosteroid or a topical anesthetic. If the itching affects their sleep, the doctor may prescribe an antihistamine, such as cetirizine (Zyrtec) or diphenhydramine (Benadryl). Medicated creams may be prescribed to help manage itchy skin or rashes. In some cases of rash, antibiotics may be prescribed.

Early treatment may improve your patients’ symptoms, so encourage them to contact the treatment team at the first sign of a reaction.


Depression is a common side effect of cancer and its treatment. It can affect mood, behavior, and ability to think and concentrate, as well as initiate physical symptoms including fatigue, loss of appetite, difficulty falling asleep or extreme tiredness. Some treatments are associated with mood changes, such as depression, suicidal thoughts or other psychiatric conditions. If your patients notice any mood changes that develop as part of their treatment, recommend that they call the physician’s office.  

It is very important to discuss any concerns the patient may have about potential side effects before their treatment starts. Communication between your health care team and the patient is crucial for managing side effects during immunotherapy. Provide patients with a list of whom to contact if they have urgent questions or if side effects develop, especially after normal office hours.

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