MedicalResearch.com: 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.
MedicalResearch.com: 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.
MedicalResearch.com: 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
MedicalResearch.com: 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
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