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.
Competing Interests: Competing interests: MO received education grants from Leenaards Foundation. ME and JT declare no conflicts of interest. SP received education grants, provided consultation, attended advisory boards and/or provided lectures for the following organizations: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, F. Hoffmann-La Roche, Janssen, Merck Sharp and Dohme, Novartis, Merck Serono, Pfizer, Regeneron and Takeda. JH received research grants from Novartis, MSD, BMS and Neon Therapeutics, and provided consultation, lectures or attended advisory boards for Amgen, AstraZeneca, Bayer, BMS, Celsius Therapeutics, Gadeta, GSK, Immunocore, MSD, Merck Serono, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi and Seattle Genetics. YW serves as consultant for Tillotts Pharma. JL received institutional research support for: BMS, MSD, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, Aveo, NIHR RM/ICR Biomedical Research Center for cancer and consultancy from: Achilles, AZ, Boston Biomedical, BMS, Eisai, EUSA Pharma, GSK, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche / Genentech, Secarna, Vitaccess. PG provided unrelated consultation and advisory board (within 2 years) for Merck, Bristol-Myers Squibb, AstraZeneca, Clovis Oncology, EMD Serono, Seattle Genetics, Foundation Medicine, Driver, Pfizer, QED Therapeutics, HERON Therapeutics, Janssen, Bayer, Genzyme, Mirati Therapeutics, Exelixis, Roche, Glaxo Smith Kline. AM advisory board member for BMS, MSD, Novartis, Roche, Pierre-Fabre.
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