Description
- Abstract:
- Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, but are associated with immune-related adverse events (irAEs). While the spectrum of single-organ irAEs has been relatively well described, the incidence, patterns, and risk factors for multi-organ system irAEs remain poorly defined. Multi-system involvement poses unique clinical challenges, often requiring prolonged immunosuppression and impacting treatment outcomes. This study characterizes the frequency and clinical features of multi-system irAEs in a large institutional cohort. Methods: We conducted a retrospective chart review of 2,134 patients with metastatic cancer treated with at least one ICI at Brown University Health between 2015 and 2025. IrAEs were identified and categorized by affected organ system. Multi-system irAEs were defined as events involving ≥2 distinct organ systems, and their frequency was stratified by sex, cancer type, and treatment regimen (monotherapy, chemo-combination, or dual-ICI). Comparisons between subgroups were performed using Fisher’s exact tests. Multivariable logistic regression was used to identify independent predictors of multi-system irAEs, with results reported as odds ratios (OR) and p-values. Results: Of 2,134 patients, 24.8% (n=530) developed at least one irAE. Among these, 22.4% (n=119) had multi-system involvement, most commonly with two organ systems (16.8%, n=89) and less frequently with three or more (5.7%, n=30). The most frequent pairings were dermatitis and endocrine (10.1%, n=12), colitis and dermatitis (9.2%, n=11), colitis and pneumonitis (5.9%, n=7), dermatitis and pneumonitis (5.9%, n=7), dermatitis and hepatitis (5.0%, n=6), and pneumonitis and endocrine (5.0%, n=6), reflecting clustering across dermatologic, gastrointestinal, pulmonary, and endocrine systems. The most common single-organ irAEs overall were dermatitis (4.9%), endocrine (4.7%), colitis (4.2%), pneumonitis (4.2%), and hepatitis (2.8%). The frequency of multi-system irAE differed significantly by treatment regimen (5.1% in ICI monotherapy vs. 4.7% in “ICI + chemo” vs. 13.9% in dual ICI; p<0.001), but no significant difference by sex (5.9% in females vs. 5.3% in males, p=0.6). When stratified by cancer type, multi-system irAEs were more frequent in patients with melanoma/skin cancers (p=0.004) and genitourinary cancers (p=0.03). On multivariable logistic regression adjusting for treatment regimen, melanoma/skin cancers remained independently associated with higher odds of multi-system irAEs (OR: 1.92, p=0.03), while the association with genitourinary cancers was attenuated and no longer significant (OR: 1.37, p=0.2). Conclusions: Multi-system irAEs accounted for nearly one-quarter of all irAE cases and were enriched in melanoma/skin cancer and GU cancer, and in patients who received dual-ICI therapy. These findings highlight the need for heightened monitoring and tailored management in high-risk groups and underscore the importance of predictive tools to guide early detection and intervention for multi-system toxicity in ICI therapy.
- Notes:
- Scholarly concentration: Non-Scholarly Concentrator
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Citation
Contini, Julia, Koh, Min Jung, Trivedi, Charmi, et al.,
"Characteristics and Predictors of Multi-system Immune-Related Adverse Events in a Large Pan-Cancer Cohort: A Retrospective Analysis"
(2025).
Warren Alpert Medical School Academic Symposium.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/kwg6-q884
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Warren Alpert Medical School Academic Symposium
The Warren Alpert Medical School Academic Symposium is an annual event at Warren Alpert Medical School of Brown University that provides Year II medical students a venue to present their summer research in a poster format. Participation in the Symposium …...