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Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy

Simone M Goldinger1, Pascale Stieger1, Barbara Meier1

  • 1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 10, 2016
PubMed
Abstract

Insights

Anti-PD-1 antibodies for melanoma treatment can cause frequent skin reactions, including rashes and vitiligo. Gene expression profiling revealed these reactions are consistently similar to toxic epidermal necrolysis (TEN).

Area of Science:

  • Oncology
  • Dermatology
  • Immunology

Background:

  • Immunotherapy using antibodies against PD-1 has shown significant progress in treating various cancers, including melanoma.
  • While generally well-tolerated, these therapies can cause adverse cutaneous reactions such as pruritus, rashes, and vitiligo, which require further characterization.

Purpose of the Study:

  • To systematically assess and characterize the adverse cutaneous reactions in melanoma patients treated with anti-PD-1 antibodies.
  • To compare the observed skin reactions with other dermatological conditions like maculopapular drug rash, cutaneous GVHD, and toxic epidermal necrolysis (TEN).

Main Methods:

  • Patients with melanoma were treated with anti-PD-1 antibodies within clinical trials and an early-access program.
  • Adverse cutaneous eruptions were systematically investigated using histology and gene expression profiling.
  • Comparisons were made with maculopapular drug rash, cutaneous GVHD, and TEN.

Main Results:

  • Out of 68 patients with stage IV melanoma, 15 (22%) developed cutaneous reactions and 10 (15%) developed vitiligo.
  • Cutaneous reactions varied from mild rashes to severe maculopapular rashes with epidermal detachment and mucosal involvement.
  • Gene expression profiling classified all investigated cases as TEN-like reactions, irrespective of clinical presentation.

Conclusions:

  • Anti-PD-1 antibodies frequently induce adverse cutaneous reactions in melanoma patients, as suggested by PD-1 knockout mouse models.
  • The consistent TEN-like pattern observed via gene expression profiling suggests PD-1/PD-L1 interaction is crucial for maintaining epidermal integrity during inflammatory skin responses.

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