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Side Effects of Checkpoint Inhibitors: What Patients Should Know

A diagram showing various organs in the human body that can be affected by immune-related side effects from checkpoint inhibitor therapy

By Peter Teoh, Science Writer

Checkpoint inhibitors can cause typical “chemo-like” side effects (fatigue, nausea) but their hallmark is immune-related inflammation, where activated T cells attack normal organs. These effects can appear weeks to months after starting treatment and sometimes even after stopping.

Very common, often mild effects

Across melanoma, lung, kidney, bladder and other responsive cancers, common non-serious symptoms include:

  • Fatigue and low energy. cancer
  • Mild skin problems: rash, itching, dry skin, vitiligo-like light patches. cancer
  • Gastrointestinal upset: mild diarrhea, nausea, decreased appetite, abdominal discomfort. pmc.ncbi.nlm.nih
  • Mild joint and muscle aches. cancerresearch

Any organ can be inflamed; typical patterns are similar across the advanced cancers where these drugs are used:

  • Skin: more intense rash, blistering, or extensive itching; rarely severe skin reactions needing urgent care. cancercouncil.com
  • Gut (colitis): persistent or bloody diarrhea, crampy abdominal pain, fever; in severe cases risk of bowel perforation. pmc.ncbi.nlm.nih
  • Liver (hepatitis): usually picked up as raised liver enzymes on blood tests, sometimes with jaundice, dark urine, or right-upper-quadrant pain. pmc.ncbi.nlm.nih
  • Lungs (pneumonitis): dry cough, shortness of breath, chest discomfort; can be life-threatening if not recognized early. ascopubs
  • Endocrine glands:
    • Thyroiditis: hyper- then often hypothyroidism (fatigue, weight change, feeling cold, constipation, hair loss).
    • Pituitary or adrenal inflammation (hypophysitis, adrenalitis): headaches, low blood pressure, severe fatigue, nausea, electrolyte changes; often requires long-term hormone replacement. cancer
  • Joints and muscles: inflammatory arthritis or myositis with significant pain, stiffness, or weakness that can persist long term. pmc.ncbi.nlm.nih
  • Kidneys: immune-mediated nephritis causing rising creatinine and reduced kidney function, sometimes with swelling or decreased urine output. ascopubs
  • Nervous system and heart (rare but dangerous): myocarditis (chest pain, heart failure, arrhythmias), neuropathies or Guillain-Barre-like syndromes, meningitis or encephalitis. pmc.ncbi.nlm.nih

During or shortly after infusions, patients may experience:

  • Infusion reactions resembling allergy: fever, chills, flushing, rash, wheeze, shortness of breath, low blood pressure. cancer
  • Rare cytokine-release-like syndromes with high fever, low blood pressure, fast heart rate, and severe malaise. cancer

Frequency and severity patterns

  • Most patients either have no side effects or only mild ones; serious (grade 3-4) immune-related events occur in a minority but are more common with combination regimens (e.g., PD-1 + CTLA-4) than with single agents. pmc.ncbi.nlm.nih
  • Some toxicities, especially endocrine and joint problems, can become chronic and persist for years after treatment, even when the cancer is controlled. cancer

Management principles in advanced cancers

  • Mild effects are often managed with symptomatic treatment while continuing immunotherapy and close monitoring. cancerresearchuk
  • Moderate to severe organ inflammation usually requires holding the drug and starting corticosteroids; life-threatening cases may need high-dose steroids, additional immunosuppressants, and permanent discontinuation. cancerresearchuk

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