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Checkpoint Inhibitors.

Lucie Heinzerling1, Enrico N de Toni, Georg Schett

  • 1Department of Dermatology, University Hospital Erlangen-Nürnberg; Department of Internal Medicine II, University Hospital, Ludwig-Maximilians-University (LMU )Munich; Department of Medicine 3, University Hospital Erlangen-Nürnberg; Department of Medicine 1, University Hospital Erlangen-Nürnberg; Clinic for Dermatology, Essen University Hospital, University of Duisburg-Essen.

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PubMed
Summary
This summary is machine-generated.

Checkpoint inhibitor immunotherapy can cause severe autoimmune side effects affecting multiple organs. Early recognition and expert management are crucial for successful treatment and patient survival.

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Area of Science:

  • Oncology
  • Immunology
  • Dermatology
  • Gastroenterology
  • Endocrinology
  • Nephrology
  • Cardiology
  • Neurology

Background:

  • Cancer immunotherapies like checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4) improve survival but frequently induce autoimmune side effects.
  • These immune-related adverse events (irAEs) occur in 86-96% of patients, with 17-59% experiencing severe or life-threatening conditions.

Purpose of the Study:

  • To review the spectrum of autoimmune side effects induced by checkpoint inhibitors.
  • To highlight the clinical manifestations, incidence, and management strategies for these irAEs.
  • To emphasize the importance of early detection and multidisciplinary care.

Main Methods:

  • Literature review of pertinent articles.
  • Evaluation of a side-effect registry.

Main Results:

  • Checkpoint inhibitor-induced autoimmune side effects affect all organ systems, with skin lesions (46-62%), colitis (22-48%), hepatitis (7-33%), and endocrinopathies (12-34%) being most common.
  • Rarer but serious irAEs include pneumonitis (3-8%), nephritis (1-7%), cardiotoxicity (5%), and neurological effects (1-5%).
  • Severe irAEs occur in 17-59% of patients, varying by treatment regimen; however, early monitoring and treatment are generally successful, with endocrine irAEs often requiring long-term hormone replacement.

Conclusions:

  • Management of irAEs requires coordinated care in specialized centers, ideally with an interdisciplinary "tox team."
  • Prospective registry studies are needed for structured documentation and improved understanding of irAEs in routine clinical practice.
  • Discontinuation of checkpoint inhibitors due to irAEs does not negatively impact melanoma response or patient survival.