Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

J Cutan Pathol. 2017 Feb;44(2):158-176. doi: 10.1111/cup.12858. Epub 2016 Dec 21.

Abstract

Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti-PD-1 and of 556 patients receiving anti-PD-L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti-PD-1/PD-L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient care.

Keywords: anti-CTLA-4; anti-PD-1; anti-PD-L1; dermatologic toxicities; immune checkpoint antibody.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Drug Eruptions / etiology
  • Drug Eruptions / pathology*
  • Humans
  • Ipilimumab
  • Nivolumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Ipilimumab
  • Nivolumab
  • pembrolizumab