Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies

Ann Oncol. 2015 Dec;26(12):2375-91. doi: 10.1093/annonc/mdv383. Epub 2015 Sep 14.


Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.

Keywords: adverse event; anti-PD-1; anti-PD-L1; immune checkpoint antibody; toxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology*
  • Exanthema / chemically induced
  • Fatigue / chemically induced
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Pneumonia / chemically induced
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology*


  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human
  • Programmed Cell Death 1 Receptor