American Melanoma Institute · 5 min read
How checkpoint inhibitors can inflame healthy organs, the symptoms that need a same-day call, how steroids treat them, and which effects are permanent.
Checkpoint inhibitors such as pembrolizumab, nivolumab, ipilimumab and relatlimab take a brake off the immune system so it can attack melanoma. The same released immune cells sometimes attack healthy tissue. Doctors call these reactions immune-related adverse events, and they can involve almost any organ.
Most are mild and treatable. A few are dangerous if they go unreported for days, so cancer teams ask patients to report new symptoms quickly, even ones that seem minor.
According to the NCCN patient guideline, skin reactions usually start in the first few weeks of treatment, and bowel symptoms typically start in the first 6 to 8 weeks. They can also appear at any later point, including after the last dose. NCCN advises staying alert for new symptoms for at least 1 year after immunotherapy ends.
In a pooled analysis of trials of pembrolizumab given after surgery (Luke and colleagues, European Journal of Cancer, 2024), about 36% of patients had an immune-related side effect, and in about 9% it was severe. Rates are higher when 2 checkpoint inhibitors are combined, as with ipilimumab plus nivolumab.
Skin: a rash of flat red patches and small bumps, often itchy. Steroid creams handle most cases. Blisters, peeling skin, or sores in the mouth need urgent attention.
Gut: inflammation of the colon, called colitis, causes watery diarrhea, cramping, urgency, and sometimes blood or mucus in the stool. Count your bowel movements. An increase of several a day over your normal pattern is worth a call, and the team should hear about it before you cover it up with anti-diarrhea medicine.
Liver: hepatitis from immunotherapy usually causes no symptoms at all. Routine blood tests before each dose catch it as a rise in liver enzymes. Yellow skin or eyes, dark urine, or pain under the right ribs are late signs.
Lungs: pneumonitis is inflammation of the lung tissue. It shows up as a new dry cough, shortness of breath, chest pain, or fever.
The thyroid is the gland affected most often. It may briefly release too much hormone and then become underactive, which brings fatigue, weight gain, dry skin, constipation, and feeling cold.
Inflammation of the pituitary gland (hypophysitis) is more common with ipilimumab. It causes headache, deep fatigue, weakness, loss of appetite, and sometimes vision changes. When the pituitary fails, the adrenal glands stop making cortisol, the hormone the body needs to handle illness and stress. A severe cortisol shortage, called adrenal crisis, causes low blood pressure, vomiting and confusion, and needs hospital care.
Type 1 diabetes is rare, affecting fewer than 1 in 100 patients in pooled studies, and can arrive suddenly. Extreme thirst, frequent urination, weight loss, nausea, or fruity-smelling breath call for a same-day blood sugar check.
Hormone problems are usually permanent, and stopping immunotherapy does not reverse them. A daily thyroid pill, hydrocortisone tablets, or insulin replaces what the gland no longer makes, and cancer treatment can often continue.
These reactions are uncommon and the most serious. Myocarditis, inflammation of the heart muscle, causes chest pain or pressure, shortness of breath, a racing or irregular heartbeat, or fainting.
Nerve and muscle reactions include conditions that resemble myasthenia gravis and Guillain-Barré syndrome, along with inflammation of the brain or its lining. Warning signs are drooping eyelids, double vision, trouble swallowing, new weakness in the arms or legs, numbness that spreads, severe headache with a stiff neck, or confusion. All of these need hospital evaluation.
Use the oncology clinic's 24-hour number instead of waiting for the next visit. If you go to an emergency room, say right away that you are on immunotherapy or had it in the past year.
Mild reactions may need only a cream or a short pause in treatment. For moderate and severe reactions, the main treatment is a corticosteroid such as prednisone or methylprednisolone, which quiets the immune attack. Severe cases are treated in the hospital with steroids through a vein.
Steroids are then reduced slowly over several weeks. This is called a taper, and stopping suddenly can let the inflammation rebound. If steroids do not work, doctors add a second immune-suppressing drug. Infliximab is the usual choice for colitis, and mycophenolate or immune globulin (IVIG) is used for some other organs.
Hormone gland problems are the exception: doctors treat them by replacing the missing hormone, and steroids do not restore the gland. Whether immunotherapy restarts after a reaction depends on which organ was involved and how severe it was. After myocarditis or a serious nerve reaction, doctors usually stop the drug for good.
NCCN advises asking your care team for an immunotherapy wallet card. It names the drug you receive, lists possible side effects, and gives your oncology team's phone numbers. Emergency staff may not think of immunotherapy when they see diarrhea or a cough, and the treatment differs from what they would give for an infection.
Keep the card with you for at least 1 year after your last dose. People who take hydrocortisone for adrenal insufficiency should also ask about a medical alert bracelet, because they need extra steroid doses during illness, injury or surgery.
