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. 2025 Aug 4;30(8):oyae318.
doi: 10.1093/oncolo/oyae318.

Management of severe immune-related adverse events and outcomes in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors

Jarushka Naidoo  1   2   3 , Douglas B Johnson  4 , Charlotte Doran  5 , Yuexi Wang  5 , Yan Zhang  6 , Trong Kim Le  6 , Sari Hopson  6 , Brian Dreyfus  6 , Lincy S Lal  5 , Charmy Vyas  6 , Shay Goldstein  6 , Zara Izadi  6
Affiliations

Management of severe immune-related adverse events and outcomes in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors

Jarushka Naidoo et al. Oncologist. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) are associated with severe immune-related adverse events (s-irAEs) that result in hospitalization, emergency department (ED) visits, treatment discontinuation, or death. This study examined the impact of s-irAEs and their earliest management strategies on clinical outcomes in advanced non-small cell lung cancer (NSCLC).

Methods: Data were derived from ConcertAI Patient360 NSCLC, a US-based electronic medical record database, between January 2012 and May 2021. Eligible patients had advanced NSCLC and received ICI-containing therapy. s-irAEs and management actions were abstracted from unstructured EHR data from ICI initiation through the earliest of 100 days after ICI discontinuation, start of a non-ICI-containing regimen, loss to follow up, end of study period, or death. Multivariable Cox regression analysis was used to evaluate the association between s-irAEs and their earliest management strategies, and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS).

Results: The study included 3211 patients. Median (IQR) age was 67 (60-73) years, and 44.9% were female. Most patients (61.6%) initiated ICIs as first-line therapy; half (50.1%) initiated ICIs as monotherapy, with nivolumab monotherapy (29.5%) as the most common initial ICI-containing regimen in any line. Overall, 8.6% of patients experienced s-irAEs, most often diarrhea (3.5%), pneumonitis (1.4%), and rash (1.3%). Among patients who experienced at least one s-irAEs, over half (57.4%) were hospitalized, and 71.8% were treated with corticosteroids, any time after the occurrence of their first s-irAEs. Median rwPFS was 4.9 (95%CI, 4.6-5.2) months, and median rwOS was 13.6 (12.6-14.7) months from ICI initiation. rwPFS and rwOS were comparable between patients with s-irAEs vs patients without s-irAEs when s-irAEs were first managed with anti-cancer treatment interruptions. Patients with s-irAEs had a 53% (22.3%-91.4%) higher risk of death than patients without s-irAEs when s-irAEs initially required corticosteroids or other immunosuppressants, and a 61% (37.9%-87.9%) higher risk of death when s-irAEs first required hospitalization or ED admission.

Conclusion: The impact of s-irAEs on clinical outcomes may depend on the initial intervention required to manage the adverse event. s-irAEs were associated with worse outcomes when they initially required hospital/ED admission, corticosteroids, or other immunosuppression.

Keywords: adverse events management; immune checkpoint inhibitors; immune-related adverse events; non-small cell lung cancer; real-world outcomes.

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Conflict of interest statement

J.N. reports Research Funding from AstraZeneca, Bristol-Myers Squibb, Roche/Genentech, Amgen, Arcus Biosciences, and Mirati, Honoraria from AstraZeneca, Bristol-Myers Squibb, Roche/Genentech, and Daiichi Sankyo, provision of Consulting and participation on an Advisory Board/Steering Committee for AstraZeneca, Bristol-Myers Squibb, Roche/Genentech, Amgen, Arcus Biosciences, NGM Pharmaceuticals, Bayer, Regeneron, Takeda, Pfizer, Elevation Oncology, Abbvie, Kaleido Biosciences, and Daiichi Sankyo, and participation on a Data Safety Monitoring Board for AstraZeneca, Bristol-Myers Squibb, and Daiichi Sankyo. D.B.J. reports receiving Consulting Fees, and participation on a Data Safety Monitoring Board or Advisory Board for Bristol-Myers Squibb, Merck, Pfizer, Teiko, Targovax, and Iovance. C.D. and L.S.L. were employed by ConcertAI at the time this research was conducted and disclosed research funding to ConcertAI from Bristol-Myers Squibb. Y.W. is employed by ConcertAI and discloses research funding to ConcertAI from Bristol-Myers Squibb. Y.Z. was employed by Bristol-Myers Squibb at the time this research was conducted and holds stock or stock options in Bristol-Myers Squibb. Y.Z. is currently employed at Janssen. T.K.L., S.H., B.D., C.V., S.G., and Z.I. are employed by Bristol-Myers Squibb and hold stock or stock options in Bristol-Myers Squibb.

Figures

Figure 1.
Figure 1.
Study attrition. Abbreviation: ICI, immune checkpoint inhibitor; NSCLC, non-small cell lung cancer.
Figure 2.
Figure 2.
Study timelines. Abbreviation: aNSCLC, advanced non-small cell lung cancer; ICI, immune checkpoint inhibitor; rwOS, real-world overall survival; s-irAE, severe immune-related adverse event.
Figure 3.
Figure 3.
Kaplan-Meier analysis of (A) rwOS and (B) rwPFS from the start of ICI-containing therapy among patients with advanced NSCLC. CI, confidence interval; ICI, immune checkpoint inhibitor; NSCLC,  non-small cell lung cancer; rwOS, real-world overall survival; rwPFS, real-world progression-free survival.
See this image and copyright information in PMC

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