Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2020 Jun 1;6(6):865-871.
doi: 10.1001/jamaoncol.2020.0726.

Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer

Charles Dolladille  1 , Stéphane Ederhy  2 , Marion Sassier  3 , Jennifer Cautela  4   5   6   7   8 , Franck Thuny  4   5   6   7   8 , Ariel A Cohen  2 , Sophie Fedrizzi  3 , Basile Chrétien  3 , Angélique Da-Silva  3   9 , Anne-Flore Plane  10 , Damien Legallois  11 , Paul U Milliez  11 , Véronique Lelong-Boulouard  3 , Joachim Alexandre  1
Affiliations
Observational Study

Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer

Charles Dolladille et al. JAMA Oncol. .

Abstract

Importance: Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE).

Objective: To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences.

Design, setting, and participants: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included.

Main outcomes and measures: The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge.

Results: A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs.

Conclusions and relevance: This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Plane reported receiving consultant and lecture fees from Novartis. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Time to Onset of Initial Immune-Related Adverse Events
Squares represent the median and whiskers represent the interquartile range (IQR) of time to immune-related adverse event (irAE) onset. Square size is log-proportional to the number of cases.
Figure 2.
Figure 2.. Rate of Recurrence According to the Initial Immune-Related Adverse Event
See this image and copyright information in PMC

Comment in

References

    1. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974-1982. doi:10.1200/JCO.2014.59.4358 - DOI - PMC - PubMed
    1. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. . Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345-1356. doi:10.1056/NEJMoa1709684 - DOI - PMC - PubMed
    1. Motzer RJ, Tannir NM, McDermott DF, et al. ; CheckMate 214 Investigators . Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-1290. doi:10.1056/NEJMoa1712126 - DOI - PMC - PubMed
    1. Antonia SJ, López-Martin JA, Bendell J, et al. . Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016;17(7):883-895. doi:10.1016/S1470-2045(16)30098-5 - DOI - PubMed
    1. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158-168. doi:10.1056/NEJMra1703481 - DOI - PubMed

Publication types

Substances