Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer

E J van Dijk; M M Smeenk; F Bensch; A M Sadowksa; M V Verschueren; M Verhaert; A Llobell; Y Suzuki; D F L Liew; A Takeji; A T J Maria; B J M Peters; J S Garcia Morillo; K Chatzidionysiou; M Lidar; E C van der Hout; S Aspeslagh; G J M Herder; E M W van de Garde; L E L Hendriks; L B M Hijmering-Kappelle; W S M E Theelen; K P M Suijkerbuijk; R J Verheijden

doi:10.1016/j.esmoop.2025.106052

Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer

E J van Dijk^*
, M M Smeenk
, F Bensch
, A M Sadowksa
, M V Verschueren
, M Verhaert
, A Llobell
, Y Suzuki
, D F L Liew
, A Takeji
, A T J Maria
, B J M Peters^*
, J S Garcia Morillo
, K Chatzidionysiou
, M Lidar
, E C van der Hout
, S Aspeslagh
, G J M Herder
, E M W van de Garde
, L E L Hendriks

L B M Hijmering-Kappelle, W S M E Theelen, K P M Suijkerbuijk, R J Verheijden

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Recent studies have demonstrated that high-dose corticosteroids and second-line immunosuppressants may impair survival of patients with immune-related adverse events (irAEs) upon treatment with immune checkpoint inhibitors (ICIs). In non-small-cell lung cancer (NSCLC), this has not been studied in sufficiently powered studies. This study assessed the association of corticosteroid dose and second-line immunosuppressants for irAEs with survival outcomes in patients with stage IV NSCLC treated with ICIs.

PATIENTS AND METHODS: Patients with stage IV NSCLC treated with ICI-based regimens between 2015 and 2022 in the first or second line who received systemic immunosuppressants for irAEs were retrospectively included from 17 hospitals in eight countries worldwide. Associations of corticosteroid peak and cumulative dose, and use of second-line immunosuppressants with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression.

RESULTS: Of 419 included patients, 339 (80.9%) were treated with corticosteroids only and 80 (19.1%) received second-line immunosuppressants. Higher corticosteroid peak dose was associated with impaired OS [adjusted hazard ratio (HRadj) 1.63, 95% confidence interval (CI) 1.27-2.08 for an increase by 80 mg prednisolone equivalent] and CSS (HRadj 1.54, 95% CI 1.13-2.08), but not PFS (HRadj 1.05, 95% CI 0.75-1.48). The cumulative corticosteroid dose and use of second-line immunosuppressants were not associated with survival.

CONCLUSION: Treatment with high corticosteroid peak dose for irAEs is associated with impaired survival in patients with stage IV NSCLC receiving ICI. Treatment of severe irAEs often requires high doses of corticosteroids. However, clinicians should weigh the unfavorable effects of high peak doses against the need for rapid irAE management.

Original language	English
Article number	106052
Number of pages	9
Journal	ESMO open
Volume	11
Issue number	2
Early online date	20 Jan 2026
DOIs	https://doi.org/10.1016/j.esmoop.2025.106052
Publication status	Published - Feb 2026

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Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancerFinal published version, 528 KBLicence: CC BY

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van Dijk, E. J., Smeenk, M. M., Bensch, F., Sadowksa, A. M., Verschueren, M. V., Verhaert, M., Llobell, A., Suzuki, Y., Liew, D. F. L., Takeji, A., Maria, A. T. J., Peters, B. J. M., Garcia Morillo, J. S., Chatzidionysiou, K., Lidar, M., van der Hout, E. C., Aspeslagh, S., Herder, G. J. M., van de Garde, E. M. W., ... Verheijden, R. J. (2026). Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer. ESMO open, 11(2), Article 106052. https://doi.org/10.1016/j.esmoop.2025.106052

@article{c780f27b3d784a5aaa3368676760c7e4,

title = "Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer",

abstract = "BACKGROUND: Recent studies have demonstrated that high-dose corticosteroids and second-line immunosuppressants may impair survival of patients with immune-related adverse events (irAEs) upon treatment with immune checkpoint inhibitors (ICIs). In non-small-cell lung cancer (NSCLC), this has not been studied in sufficiently powered studies. This study assessed the association of corticosteroid dose and second-line immunosuppressants for irAEs with survival outcomes in patients with stage IV NSCLC treated with ICIs.PATIENTS AND METHODS: Patients with stage IV NSCLC treated with ICI-based regimens between 2015 and 2022 in the first or second line who received systemic immunosuppressants for irAEs were retrospectively included from 17 hospitals in eight countries worldwide. Associations of corticosteroid peak and cumulative dose, and use of second-line immunosuppressants with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression.RESULTS: Of 419 included patients, 339 (80.9\%) were treated with corticosteroids only and 80 (19.1\%) received second-line immunosuppressants. Higher corticosteroid peak dose was associated with impaired OS [adjusted hazard ratio (HRadj) 1.63, 95\% confidence interval (CI) 1.27-2.08 for an increase by 80 mg prednisolone equivalent] and CSS (HRadj 1.54, 95\% CI 1.13-2.08), but not PFS (HRadj 1.05, 95\% CI 0.75-1.48). The cumulative corticosteroid dose and use of second-line immunosuppressants were not associated with survival.CONCLUSION: Treatment with high corticosteroid peak dose for irAEs is associated with impaired survival in patients with stage IV NSCLC receiving ICI. Treatment of severe irAEs often requires high doses of corticosteroids. However, clinicians should weigh the unfavorable effects of high peak doses against the need for rapid irAE management.",

author = "\{van Dijk\}, \{E J\} and Smeenk, \{M M\} and F Bensch and Sadowksa, \{A M\} and Verschueren, \{M V\} and M Verhaert and A Llobell and Y Suzuki and Liew, \{D F L\} and A Takeji and Maria, \{A T J\} and Peters, \{B J M\} and \{Garcia Morillo\}, \{J S\} and K Chatzidionysiou and M Lidar and \{van der Hout\}, \{E C\} and S Aspeslagh and Herder, \{G J M\} and \{van de Garde\}, \{E M W\} and Hendriks, \{L E L\} and Hijmering-Kappelle, \{L B M\} and Theelen, \{W S M E\} and Suijkerbuijk, \{K P M\} and Verheijden, \{R J\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2026",

month = feb,

doi = "10.1016/j.esmoop.2025.106052",

language = "English",

volume = "11",

journal = "ESMO open",

issn = "2059-7029",

publisher = "Elsevier",

number = "2",

}

van Dijk, EJ, Smeenk, MM, Bensch, F, Sadowksa, AM, Verschueren, MV, Verhaert, M, Llobell, A, Suzuki, Y, Liew, DFL, Takeji, A, Maria, ATJ, Peters, BJM, Garcia Morillo, JS, Chatzidionysiou, K, Lidar, M, van der Hout, EC, Aspeslagh, S, Herder, GJM, van de Garde, EMW, Hendriks, LEL, Hijmering-Kappelle, LBM, Theelen, WSME, Suijkerbuijk, KPM & Verheijden, RJ 2026, 'Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer', ESMO open, vol. 11, no. 2, 106052. https://doi.org/10.1016/j.esmoop.2025.106052

TY - JOUR

T1 - Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer

AU - van Dijk, E J

AU - Smeenk, M M

AU - Bensch, F

AU - Sadowksa, A M

AU - Verschueren, M V

AU - Verhaert, M

AU - Llobell, A

AU - Suzuki, Y

AU - Liew, D F L

AU - Takeji, A

AU - Maria, A T J

AU - Peters, B J M

AU - Garcia Morillo, J S

AU - Chatzidionysiou, K

AU - Lidar, M

AU - van der Hout, E C

AU - Aspeslagh, S

AU - Herder, G J M

AU - van de Garde, E M W

AU - Hendriks, L E L

AU - Hijmering-Kappelle, L B M

AU - Theelen, W S M E

AU - Suijkerbuijk, K P M

AU - Verheijden, R J

PY - 2026/2

Y1 - 2026/2

N2 - BACKGROUND: Recent studies have demonstrated that high-dose corticosteroids and second-line immunosuppressants may impair survival of patients with immune-related adverse events (irAEs) upon treatment with immune checkpoint inhibitors (ICIs). In non-small-cell lung cancer (NSCLC), this has not been studied in sufficiently powered studies. This study assessed the association of corticosteroid dose and second-line immunosuppressants for irAEs with survival outcomes in patients with stage IV NSCLC treated with ICIs.PATIENTS AND METHODS: Patients with stage IV NSCLC treated with ICI-based regimens between 2015 and 2022 in the first or second line who received systemic immunosuppressants for irAEs were retrospectively included from 17 hospitals in eight countries worldwide. Associations of corticosteroid peak and cumulative dose, and use of second-line immunosuppressants with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression.RESULTS: Of 419 included patients, 339 (80.9%) were treated with corticosteroids only and 80 (19.1%) received second-line immunosuppressants. Higher corticosteroid peak dose was associated with impaired OS [adjusted hazard ratio (HRadj) 1.63, 95% confidence interval (CI) 1.27-2.08 for an increase by 80 mg prednisolone equivalent] and CSS (HRadj 1.54, 95% CI 1.13-2.08), but not PFS (HRadj 1.05, 95% CI 0.75-1.48). The cumulative corticosteroid dose and use of second-line immunosuppressants were not associated with survival.CONCLUSION: Treatment with high corticosteroid peak dose for irAEs is associated with impaired survival in patients with stage IV NSCLC receiving ICI. Treatment of severe irAEs often requires high doses of corticosteroids. However, clinicians should weigh the unfavorable effects of high peak doses against the need for rapid irAE management.

AB - BACKGROUND: Recent studies have demonstrated that high-dose corticosteroids and second-line immunosuppressants may impair survival of patients with immune-related adverse events (irAEs) upon treatment with immune checkpoint inhibitors (ICIs). In non-small-cell lung cancer (NSCLC), this has not been studied in sufficiently powered studies. This study assessed the association of corticosteroid dose and second-line immunosuppressants for irAEs with survival outcomes in patients with stage IV NSCLC treated with ICIs.PATIENTS AND METHODS: Patients with stage IV NSCLC treated with ICI-based regimens between 2015 and 2022 in the first or second line who received systemic immunosuppressants for irAEs were retrospectively included from 17 hospitals in eight countries worldwide. Associations of corticosteroid peak and cumulative dose, and use of second-line immunosuppressants with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression.RESULTS: Of 419 included patients, 339 (80.9%) were treated with corticosteroids only and 80 (19.1%) received second-line immunosuppressants. Higher corticosteroid peak dose was associated with impaired OS [adjusted hazard ratio (HRadj) 1.63, 95% confidence interval (CI) 1.27-2.08 for an increase by 80 mg prednisolone equivalent] and CSS (HRadj 1.54, 95% CI 1.13-2.08), but not PFS (HRadj 1.05, 95% CI 0.75-1.48). The cumulative corticosteroid dose and use of second-line immunosuppressants were not associated with survival.CONCLUSION: Treatment with high corticosteroid peak dose for irAEs is associated with impaired survival in patients with stage IV NSCLC receiving ICI. Treatment of severe irAEs often requires high doses of corticosteroids. However, clinicians should weigh the unfavorable effects of high peak doses against the need for rapid irAE management.

U2 - 10.1016/j.esmoop.2025.106052

DO - 10.1016/j.esmoop.2025.106052

M3 - Article

C2 - 41564819

SN - 2059-7029

VL - 11

JO - ESMO open

JF - ESMO open

IS - 2

M1 - 106052

ER -

Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer

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