Spectrum and effect sizes (any grade and grade 3 or higher) of immune checkpoint inhibitor (ICI)-related adverse events, categorized by organ system/type, as reported in a systematic review and meta-analysis by Dang et al. [48]

Adverse event categorySpecific adverse eventsEffect size (%)*, (any grade)Effect size (%), (grade 3 or higher)
FatigueRanging from mild to severe intensity14.950.74
Dermatological reactionsRash, pruritus (itching), vitiligo, erythema, dermatitis

  • Rash: 8.66;

  • Pruritus: 7.5

  • Rash: 0.26;

  • Pruritus: rare

Gastrointestinal issuesDiarrhea, colitis, nausea, vomiting, abdominal pain

  • Diarrhea: 6.77;

  • Nausea: 5.57;

  • Vomiting: 2.49;

  • Colitis: 0.62

  • Diarrhea: 0.35;

  • Nausea: very rare;

  • Vomiting: very rare;

  • Colitis: 0.34

EndocrinopathiesHypothyroidism, hyperthyroidism, adrenal insufficiency, diabetes mellitus, hypophysitis

  • Hypothyroidism: 11.21;

  • Hyperthyroidism: 3.29

  • Hypothyroidism: very rare;

  • Hyperthyroidism: rare

HepatotoxicityElevated liver enzymes, autoimmune hepatitis, jaundice

  • Hepatitis: 1.97;

  • AST increased: 4.75;

  • ALT increased: 3.48

  • Hepatitis: 1.13;

  • AST increased: 0.65;

  • ALT increased: 0.19

Pulmonary toxicityPneumonitis, interstitial lung diseasePneumonitis: 2.92Pneumonitis: 0.95
Renal toxicityNephritis, acute kidney injuryNephritis: 0.51Nephritis: 0.30
Neurological issuesPeripheral neuropathy, encephalitis, Guillain-Barre syndrome, myasthenia gravisNeuropathy: 1.02Neuropathy: 0.04
Hematological toxicityThrombocytopenia, pancytopenia or immune aplastic anemia, neutropenia, anemia, cytokine release syndrome with hemophagocytic syndrome

  • Thrombocytopenia: 2.46;

  • Anemia: 4.73

  • Thrombocytopenia: 0.50;

  • Anemia: 0.67

* Data were pooled from 20 clinical trials involving 3,756 patients with recurrent or metastatic head and neck squamous cell carcinoma. Pooled incidences of specific adverse events reported in at least two studies are shown. Adverse events are classified as rare (< 0.1%, ≥ 0.01%) or very rare (< 0.01%). AST: aspartate aminotransferase; ALT: alanine aminotransferase