Immune Checkpoint Inhibitor Re-Challenge in Patients Who Develop Severe Immune-Related Adverse Events - Expert Commentary

Treating patients who received immune checkpoint inhibition (ICI) and experienced treatment-related toxicities, remains complicated due to the high risk of Immune-relate adverse events (irAEs) with the reintroduction of ICIs.

A recent review published by Haanen et al. in the Journal for ImmunoTherapy of Cancer reviewed the published literature to identify strategies for reintroducing ICIs. The investigators examined three scenarios for reintroducing ICIs: class switching, ICI re-challenge with the same class or same molecule, and ICI resumption concomitant with immunosuppressive therapy. The authors reviewed two retrospective studies in melanoma patients, suggesting that switching from anti-CTLA-4 to anti-PD-1 in patients with previous anti-CTLA-4-related severe irAEs may be feasible. Regarding the challenging strategy, a study of anti-PD-1 re-challenge in 80 melanoma patients showed that 39% (n=31) of patients experienced clinically significant recurrent or distinct toxicities. In this study, colitis was less likely to recur than other irAEs (6% vs. 28%). The authors reviewed another series of 38 non-small cell lung cancer patients who were switched to another drug in the same class. In this study, after retreatment, 10 (26%) patients experienced recurrence of the initial irAE, and 10 (26%) had a new irAE. Most recurrent or new irAEs were mild. The authors review several patient case series supporting the feasibility of the resumption strategy. Interestingly, in one study of 167 patients, the rate of immune-mediated diarrhea and colitis recurrence was significantly lower when PD-L1 rather than CTLA-4 inhibitors were used for ICI resumption. Finally, for the ICI resumption concomitant with immunosuppressive therapy, limited conclusions could be made from the small case series.

The authors provide an expert-based framework for resuming ICIs in selected cases with a variety of secondary prevention strategies. They acknowledge the limitations of the available evidence and call for prospective trials.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. 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.
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