TY - JOUR
T1 - Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma
AU - Verheijden, Rik J.
AU - Burgers, Femke H.
AU - Janssen, Josephine C.
AU - Putker, Anouk E.
AU - Veenstra, Sophie P.G.R.
AU - Hospers, Geke A.P.
AU - Aarts, Maureen J.B.
AU - Hehenkamp, Karel W.
AU - Doornebosch, Veerle L.E.
AU - Verhaert, Marthe
AU - van den Berkmortel, Franchette W.P.J.
AU - Chatzidionysiou, Katerina
AU - Llobell, Arturo
AU - Barros, Milton
AU - Maria, Alexandre T.J.
AU - Takeji, Akari
AU - García Morillo, José Salvador
AU - Lidar, Merav
AU - van Eijs, Mick J.M.
AU - Blank, Christian U.
AU - Aspeslagh, Sandrine
AU - Piersma, Djura
AU - Kapiteijn, Ellen
AU - Labots, Mariette
AU - Boers-Sonderen, Marye J.
AU - van der Veldt, Astrid A.M.
AU - Haanen, John B.A.G.
AU - May, Anne M.
AU - Suijkerbuijk, Karijn P.M.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/8
Y1 - 2024/8
N2 - Background: 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. Methods: 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. Results: 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 (HRadj 1.14; 95 %CI 1.01–1.29; HRadj 1.29; 95 %CI 1.12–1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02–1.72) and OS (HRadj 1.34; 95 %CI 0.99–1.82) compared with corticosteroids alone. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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 (HRadj 1.14; 95 %CI 1.01–1.29; HRadj 1.29; 95 %CI 1.12–1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02–1.72) and OS (HRadj 1.34; 95 %CI 0.99–1.82) compared with corticosteroids alone. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85196413135&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2024.114172
DO - 10.1016/j.ejca.2024.114172
M3 - Article
C2 - 38905818
AN - SCOPUS:85196413135
SN - 0959-8049
VL - 207
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 114172
ER -
