Titre
Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Verheijden, R.J.
Auteure/Auteur
Burgers, F.H.
Auteure/Auteur
Janssen, J.C.
Auteure/Auteur
Putker, A.E.
Auteure/Auteur
Veenstra, SPGR
Auteure/Auteur
Hospers, GAP
Auteure/Auteur
Aarts, MJB
Auteure/Auteur
Hehenkamp, K.W.
Auteure/Auteur
Doornebosch, VLE
Auteure/Auteur
Verhaert, M.
Auteure/Auteur
van den Berkmortel, FWPJ
Auteure/Auteur
Chatzidionysiou, K.
Auteure/Auteur
Llobell, A.
Auteure/Auteur
Barros, M.
Auteure/Auteur
Maria, ATJ
Auteure/Auteur
Takeji, A.
Auteure/Auteur
García Morillo, J.S.
Auteure/Auteur
Lidar, M.
Auteure/Auteur
van Eijs, MJM
Auteure/Auteur
Blank, C.U.
Auteure/Auteur
Aspeslagh, S.
Auteure/Auteur
Piersma, D.
Auteure/Auteur
Kapiteijn, E.
Auteure/Auteur
Labots, M.
Auteure/Auteur
Boers-Sonderen, M.J.
Auteure/Auteur
van der Veldt, AAM
Auteure/Auteur
Haanen, JBAG
Auteure/Auteur
May, A.M.
Auteure/Auteur
Suijkerbuijk, KPM
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1879-0852
Statut éditorial
Publié
Date de publication
2024-08
Volume
207
Première page
114172
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study
Publication Status: ppublish
Publication Status: ppublish
Résumé
Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs.
Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression.
Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4-8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4-14) and 55 (95 %CI 41-not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HR <sub>adj</sub> 1.14; 95 %CI 1.01-1.29; HR <sub>adj</sub> 1.29; 95 %CI 1.12-1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HR <sub>adj</sub> 1.32; 95 %CI 1.02-1.72) and OS (HR <sub>adj</sub> 1.34; 95 %CI 0.99-1.82) compared with corticosteroids alone.
High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression.
Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4-8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4-14) and 55 (95 %CI 41-not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HR <sub>adj</sub> 1.14; 95 %CI 1.01-1.29; HR <sub>adj</sub> 1.29; 95 %CI 1.12-1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HR <sub>adj</sub> 1.32; 95 %CI 1.02-1.72) and OS (HR <sub>adj</sub> 1.34; 95 %CI 0.99-1.82) compared with corticosteroids alone.
High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
Sujets
PID Serval
serval:BIB_AB4D3ADF8F4A
PMID
Open Access
Oui
Date de création
2024-06-28T09:49:57.600Z
Date de création dans IRIS
2025-05-20T22:37:21Z
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Nom
38905818.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
692.39 KB
Format
Adobe PDF
PID Serval
serval:BIB_AB4D3ADF8F4A.P001
URN
urn:nbn:ch:serval-BIB_AB4D3ADF8F4A8
Somme de contrôle
(MD5):e34e41213d91ecdd1395f62081118346