Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_AB4D3ADF8F4A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma.
Journal
European journal of cancer
Author(s)
Verheijden R.J., Burgers F.H., Janssen J.C., Putker A.E., Veenstra SPGR, Hospers GAP, Aarts MJB, Hehenkamp K.W., Doornebosch VLE, Verhaert M., van den Berkmortel FWPJ, Chatzidionysiou K., Llobell A., Barros M., Maria ATJ, Takeji A., García Morillo J.S., Lidar M., van Eijs MJM, Blank C.U., Aspeslagh S., Piersma D., Kapiteijn E., Labots M., Boers-Sonderen M.J., van der Veldt AAM, Haanen JBAG, May A.M., Suijkerbuijk KPM
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
08/2024
Peer-reviewed
Oui
Volume
207
Pages
114172
Language
english
Notes
Publication types: Journal Article ; Multicenter Study
Publication Status: ppublish
Abstract
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.
Keywords
Humans, Male, Female, Melanoma/drug therapy, Melanoma/immunology, Melanoma/mortality, Immunosuppressive Agents/adverse effects, Immunosuppressive Agents/therapeutic use, Immune Checkpoint Inhibitors/adverse effects, Middle Aged, Aged, Adrenal Cortex Hormones/therapeutic use, Adrenal Cortex Hormones/adverse effects, Adult, Retrospective Studies, Skin Neoplasms/drug therapy, Skin Neoplasms/immunology, Skin Neoplasms/mortality, Aged, 80 and over, Checkpoint inhibitor, Corticosteroids, Immune-related adverse events, Immunosuppression, Melanoma, Toxicity
Pubmed
Web of science
Open Access
Yes
Create date
28/06/2024 10:49
Last modification date
29/10/2024 7:21
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