Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study

J Am Acad Dermatol. 2018 Dec;79(6):1047-1052. doi: 10.1016/j.jaad.2018.05.035. Epub 2018 May 29.

Abstract

Background: Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.

Objective: To assess the nature of dermatitis after exposure to a PD-1/PD-L1 inhibitor and oncologic outcomes associated with dermatitis.

Methods: Retrospective, matched, case-control study conducted at a single academic center.

Results: The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). The overall tumor response rate was 65.0% for the case patients and 17.0% for the controls (P = .0007) (odds ratio, 7.3; 95% confidence interval, 2.3-23.1). The progression-free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan-Meier analysis (P < .0001 and .0203, respectively).

Limitations: The retrospective design and relatively small sample size precluded matching for all cancer types.

Conclusions: Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The value of PD-1/PD-L1-related dermatitis in predicting cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.

Keywords: PD-1; PD-L1; checkpoint inhibitor; dermatitis; immunotherapy; inhibitor; lichenoid; nonmelanoma skin cancer; programmed death 1; programmed death ligand 1; reaction pattern; spongiotic.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors*
  • Case-Control Studies
  • Disease-Free Survival
  • Drug Eruptions / etiology*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lichenoid Eruptions / chemically induced
  • Male
  • Middle Aged
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Nivolumab / adverse effects*
  • Nivolumab / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • atezolizumab
  • pembrolizumab