Clinical characteristics and therapies of multi-organ immune related adverse events.

Journal: Clinical and experimental medicine

This publication is a large case-based systematic analysis of immune checkpoint inhibitor (ICI)–associated immune-related adverse events (irAEs), with a specific focus on multi-organ involvement.

Design and methods

  • Data source: Case reports of ICI-related irAEs from PubMed, Web of Science, Cochrane Library, and Embase up to January 2022.
  • Population: 2,964 patients with irAEs, including 782 with multi-organ irAEs and 2,182 with single-organ irAEs.
  • Comparisons:
    • Multi-organ vs single-organ irAEs: baseline characteristics, toxicity patterns, severity, outcomes.
    • Within multi-organ irAEs: high- vs low-dose glucocorticoids, separately for severe and non-severe cases.
    • Multivariable analysis: identification of mortality-associated organ toxicities.

Key findings

1. Frequency and phenotype of multi-organ irAEs

  • Proportion: Multi-organ irAEs constituted roughly one quarter of reported irAEs.
  • Demographics: No significant age or sex differences vs single-organ cases.
  • Toxicity profile:
    • Higher rates of cardiovascular, thyroid, and skin toxicities.
    • Higher proportion of severe adverse reactions.
    • Higher overall mortality.

2. Common organ combinations

Frequent multi-organ constellations included:

  • Cardiac + neurological
  • Cardiac + pulmonary
  • Thyroid + pituitary
  • Cardiac + hepatic
  • Gastrointestinal + skin

These patterns underscore the clustering of cardiac toxicity with other critical-organ events and of endocrine toxicities with each other.

3. Glucocorticoid dosing and outcomes

Severe multi-organ irAEs:

  • No age or sex differences between high-dose and low-dose steroid groups.
  • High-dose glucocorticoids were associated with significantly higher mortality.

Non-severe multi-organ irAEs:

  • No significant differences in mortality, prognosis, age, or sex between high- and low-dose glucocorticoid groups.

Taken together, escalated steroid dosing did not confer a prognostic advantage and may be harmful in severe multi-organ irAEs.

4. Mortality risk factors

On multivariate logistic regression in multi-organ irAEs, the following organ toxicities were independently associated with higher mortality (OR > 1, statistically significant):

  • Cardiovascular toxicity
  • Pulmonary toxicity
  • Hepatotoxicity
  • Myositis

These toxicities mark a particularly high-risk subgroup.

Clinical implications for oncology practice

  • Multi-organ irAEs represent a clinically distinct, higher-risk phenotype with greater severity and mortality than single-organ irAEs.
  • Cardiac, pulmonary, hepatic, and muscular (myositis) involvement should trigger heightened concern, intensive monitoring, and early multidisciplinary input.
  • More steroid is not necessarily better: in severe multi-organ irAEs, high-dose glucocorticoids were associated with worse survival, arguing for individualized dosing rather than reflexive maximal dosing.
  • For non-severe multi-organ irAEs, high-dose steroids did not improve outcomes, suggesting lower doses may be adequate in many cases.

Overall, the study supports risk-adapted management of ICI toxicities, with careful attention to organ pattern and severity, and challenges the assumption that more aggressive steroid therapy uniformly improves outcomes in severe multi-organ irAEs.

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