Some Patients Can Be Rechallenged After Immune Adverse Events from Checkpoint Inhibitors Interview with:
Prof. Olivier Lambotte, MD, PHD Professor of Internal Medicine Paris XI University Medical School Research Director Control of Chronic Viral Infections DepartmentProf. Olivier Lambotte, MD, PHD
Professor of Internal Medicine
Paris XI University Medical School
Research Director
Control of Chronic Viral Infections Department What is the background for this study? What are the main findings? 

Response: Immune checkpoint inhibitors (ICIs) anti-programmed death-1 (PD-1) or anti-programmed death ligand-1 (PD-L1) have proven efficacy in the treatment of many cancers but patients may experience immune-related adverse events (irAEs). Immune checkpoint inhibitors is usually stopped when grade 2 or higher irAE occur. Data are very limited  on the safety of resuming treatment after such an event.

We  studied all adult patients referred to the ImmunoTOX toxicity review board at the Gustave Roussy cancer center (Villejuif, France) in 2015-2017 with  irAE grade 2 or higher for whom the  rechallenge was questioned. Among 93 patients with a broad spectrum of cancers, 40 patients (43%) were rechallenged with the same anti-PD-1 or anti-PD-L1. The rechallenged and non-rechallenged groups did not differ in terms of age, time to initial irAE, irAE severity, or steroid use. With a median follow-up period of 14 months, the same irAE or a different irAE occurred in 22 patients (55%). The second irAEs were not more severe than the first. Earlier initial toxicity was associated with more frequent irAE recurrence. What should readers take away from your report?

Response: The risk reward ratio for an anti-PD-1 rechallenge appears to be acceptable. A close monitoring is necessary. Myocarditis and severe neurologic toxicities should remain rechallenge contraindication. What recommendations do you have for future research as a result of this work?

Response: The rechallenge conditions require to be investigated in prospective clinical trials. Robust predictive factors for irAE are still lacking Is there anything else you would like to add?

Response: Rechallenge is a good example of the importance to set up multidisciplinary boards to assess the management of severe irAEs and to discuss to rechallenge or not.


Simonaggio A, Michot JM, Voisin AL, et al. Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer. JAMA Oncol. Published online June 06, 2019. doi:10.1001/jamaoncol.2019.1022

Jun 7, 2019 @ 1:39 pm

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