Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy

J Immunother Cancer. 2020 Jun;8(1):e000604. doi: 10.1136/jitc-2020-000604.


Patients with cancer who developed severe, grade 3 or 4 immune-related adverse events (irAEs) during therapy with immune checkpoint inhibitors are at risk for developing severe toxicities again on rechallenge with checkpoint inhibitors. Consequently, medical oncologists and multidisciplinary teams are hesitant to retreat in this scenario, despite the fact that a number of patients may derive clinical benefit from this approach. Balancing such clinical benefit and treatment-related toxicities for each patient is becoming increasingly challenging as more and more patients with cancer are being treated with checkpoint inhibitors. In this manuscript, we provide an extensive overview of the relevant literature on retreatment after toxicity, and suggest prophylactic approaches to minimize the risk of severe irAE following rechallenge with immune checkpoint blockade, since treatment may be lifesaving in a number of occasions.

Keywords: autoimmunity.

Publication types

  • Review

MeSH terms

  • Clinical Decision-Making*
  • Drug-Related Side Effects and Adverse Reactions / immunology*
  • Drug-Related Side Effects and Adverse Reactions / prevention & control
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Patient Selection*
  • Progression-Free Survival
  • Retreatment / adverse effects
  • Retreatment / methods
  • Risk Assessment
  • Severity of Illness Index


  • Immune Checkpoint Inhibitors