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Circulating Cytokines Predict Immune-Related Toxicity in Melanoma Patients Receiving Anti-PD-1-Based Immunotherapy

Su Y Lim1,2, Jenny H Lee1,2, Tuba N Gide2,3

  • 1Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|November 10, 2018
PubMed
Abstract

Insights

A new CYTOX score predicts severe immune-related toxicity in melanoma patients receiving combination immunotherapy. This cytokine-based score aids in early management of potentially life-threatening side effects.

Area of Science:

  • Oncology
  • Immunology
  • Biomarker Discovery

Background:

  • Combination PD-1 and CTLA-4 inhibitor therapy offers improved survival for advanced melanoma patients.
  • This treatment approach is associated with significant immune-related toxicities.
  • Identifying biomarkers for treatment response and toxicity is crucial.

Purpose of the Study:

  • To identify circulating cytokine biomarkers predictive of treatment response and immune-related toxicity in melanoma patients.
  • To develop and validate a predictive score for severe immune-related toxicity.

Main Methods:

  • Longitudinal profiling of 65 cytokines in 98 patients treated with PD-1 inhibitors (alone or combined with anti-CTLA-4).
  • Validation in an independent cohort of 49 patients on combination anti-PD-1 and anti-CTLA-4 therapy.
  • Correlation of cytokine expression with RECIST response and immune-related toxicity.

Main Results:

  • Eleven cytokines were significantly upregulated in patients with severe immune-related toxicities at baseline and early treatment.
  • A CYTOX (cytokine toxicity) score integrating these 11 cytokines was developed.
  • The CYTOX score demonstrated predictive utility in both discovery and validation cohorts (AUC 0.68-0.70).

Conclusions:

  • The CYTOX score predicts severe immune-related toxicity in melanoma patients receiving combination anti-CTLA-4 and anti-PD-1 immunotherapy.
  • This score, incorporating cytokines like IL1a, IL2, and IFNα2, can aid in early management of severe toxicities.
  • Early identification of patients at risk for severe toxicity may improve clinical outcomes.

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