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Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events

Background Rheumatic immune-related adverse events (R-irAEs) occur in 5-15% of patients receiving immune checkpoint inhibitors (ICI) and, unlike other irAEs, tend to be chronic. Herein, we investigate the factors influencing cancer and R-irAEs outcomes with particular focus on adverse effects of ant...

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Hauptverfasser: Gente, Karolina (VerfasserIn) , Diekmann, Leonore (VerfasserIn) , Daniello, Lea (VerfasserIn) , Will, Julia (VerfasserIn) , Feißt, Manuel (VerfasserIn) , Olsavszky, Victor (VerfasserIn) , Günther, Janine (VerfasserIn) , Lorenz, Hanns-Martin (VerfasserIn) , Souto-Carneiro, Maria Margarida (VerfasserIn) , Hassel, Jessica C. (VerfasserIn) , Christopoulos, Petros (VerfasserIn) , Leipe, Jan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 19, 2023
In: Journal for ImmunoTherapy of Cancer
Year: 2023, Jahrgang: 11, Heft: 9, Pages: 1-15
ISSN:2051-1426
DOI:10.1136/jitc-2023-007557
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1136/jitc-2023-007557
Verlag, kostenfrei, Volltext: https://jitc.bmj.com/content/11/9/e007557
Volltext
Verfasserangaben:Karolina Gente, Leonore Diekmann, Lea Daniello, Julia Will, Manuel Feisst, Victor Olsavszky, Janine Günther, Hanns-Martin Lorenz, M. Margarida Souto-Carneiro, Jessica C. Hassel, Petros Christopoulos, Jan Leipe
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Zusammenfassung:Background Rheumatic immune-related adverse events (R-irAEs) occur in 5-15% of patients receiving immune checkpoint inhibitors (ICI) and, unlike other irAEs, tend to be chronic. Herein, we investigate the factors influencing cancer and R-irAEs outcomes with particular focus on adverse effects of anti-inflammatory treatment. - Methods In this prospective, multicenter, long-term, observational study, R-irAEs were comprehensively analyzed in patients with malignant melanoma (MM, n=50) and non-small cell lung cancer (NSCLC, n=41) receiving ICI therapy who were enrolled in the study between August 1, 2018, and December 11, 2022. - Results After a median follow-up of 33 months, progressive disease or death occurred in 66.0% and 30.0% of MM and 63.4% and 39.0% of patients with NSCLC. Male sex (progression-free survival (PFS): p=0.013, and overall survival (OS): p=0.009), flare of a pre-existing condition (vs de novo R-irAE, PFS: p=0.010) and in trend maximum glucocorticoid (GC) doses >10 mg and particularly ≥1 mg/kg prednisolone equivalent (sex-adjusted PFS: p=0.056, OS: p=0.051) were associated with worse cancer outcomes. Patients receiving disease-modifying antirheumatic drugs (DMARDs) showed significantly longer PFS (n=14, p=0.011) and OS (n=20, p=0.018). Effects of these variables on PFS and/or OS persisted in adjusted Cox regression models. Additionally, GC treatment negatively correlated with the time from diagnosis of malignancy and the latency from ICI start until R-irAE onset (all p<0.05). R-irAE features and outcomes were independent of other baseline patient characteristics in both studied cancer entities. - Conclusion Male sex, flare of pre-existing rheumatologic conditions and extensive GC treatment appeared to be linked with unfavorable cancer outcomes, while DMARD use had a favorable impact. These findings challenge the current dogma of restrictive DMARD use for R-irAE and thus may pave the way to better strategies and randomized controlled trials for the growing number of patients with R-irAE.
Beschreibung:Online veröffentlicht: 19. September 2023
Gesehen am 27.11.2023
Beschreibung:Online Resource
ISSN:2051-1426
DOI:10.1136/jitc-2023-007557

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