ArticleJournal for immunotherapy of cancer2026
Heterogeneous survival impact of immune-related adverse events in US veterans.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundImmune-related adverse events (irAEs) have been associated with improved overall survival (OS) in patients with cancer treated with immune checkpoint inhibitors (ICIs), as irAEs are thought to signify a potentially robust antitumor immune response. The interplay between irAE subtypes, irAE severity, and oncological outcomes remains understudied.
methodsWe conducted a retrospective study of patients with cancer in the US Veteran Health Administration who received first-line or second-line ICI therapy (programmed cell death protein 1, programmed death-ligand 1, cytotoxic T-lymphocyte-associated protein 4, or lymphocyte activation gene 3 inhibitors)±chemotherapy from 2010 to 2023. Manual chart review was performed on a random sample to ascertain irAEs. The primary outcome was OS, analyzed by irAE status (no irAE vs irAE), severity (steroid-requiring vs non-steroid-requiring), and subtype (thyroid/cutaneous vs other). To account for immortal time bias, OS was analyzed with multivariable time-dependent Cox regression and 180-day landmark analysis.
resultsAmong 1707 patients, 465 (27.2%) experienced at least one irAE (median onset: 108 days; unadjusted 2-year rate: 38.2% (35%-41%)). The occurrence of any-grade irAE was not associated with improved OS (adjusted HR (aHR) 0.87; 95% CI 0.75 to 1.01). Analysis stratified by steroid requirement (n=222/465 events, 47.7%) showed improved survival with non-steroid-requiring irAE (aHR 0.69, 95% CI 0.57 to 0.84), whereas steroid-requiring irAEs were associated with a trend toward worse survival (aHR 1.13, 95% CI 0.92 to 1.38). The non-steroid-requiring irAE subset was enriched for thyroid (45% vs 8%) and cutaneous (27% vs 16%) toxicities compared with the steroid-requiring group. Exploration of the impact of irAE subtype on OS showed significant survival benefit in patients with thyroid/cutaneous irAEs (aHR 0.57, 95% CI 0.46 to 0.71) but not other irAE subtypes.
conclusionsirAEs are not uniformly associated with improved survival. Favorable outcomes are driven by thyroid-related and skin-related, non-steroid-requiring irAEs, suggesting shared biological mechanisms underlying organ-specific autoimmunity and antitumor immune response.
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