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Rechallenge Patients with Immune Checkpoint Inhibitors Following Severe Immune-Related Adverse Events: Review of the Literature and Suggested Prophylactic Strategy

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.

Authors: John Haanen,1 Marc Ernstoff,2 Yinghong Wang,3 Alexander Menzies,4,5 Igor Puzanov,2 Petros Grivas,6 James Larkin,7 Solange Peters,8 John Thompson,6 Michel Obeid9,10

  1. Netherlands Cancer Institute, Division of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
  2. Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, New York 14263, USA
  3. Department of Gastroenterology, Hepatology & Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
  4. Melanoma Institute Australia and The University of Sydney, Sydeny, New South Wales, Australia
  5. Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia
  6. University of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  7. Royal Marsden NHS Foundation Trust, London, UK
  8. Centre Hospitalier Universitaire Vaudois (CHUV), Department of Oncology, rue du Bugnon 46, CH-1011 Lausanne, Switzerland
  9. Centre Hospitalier Universitaire Vaudois (CHUV), Department of Medicine, Service of Immunology and Allergy, rue du Bugnon 46, CH-1011 Lausanne, Switzerland
  10. Centre Hospitalier Universitaire Vaudois (CHUV), Vaccine and Immunotherapy Center, rue du Bugnon 17, CH-1011 Lausanne, Switzerland
Source: Haanen, John, Marc Ernstoff, Yinghong Wang, Alexander Menzies, Igor Puzanov, Petros Grivas, James Larkin, Solange Peters, John Thompson, and Michel Obeid. "Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy." Journal for ImmunoTherapy of Cancer 8, no. 1 (2020): e000604.

Read an Expert Commentary by Bishoy Faltas, MD