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Gente, Karolina; Diekmann, Leonore; Daniello, Lea; Will, Julia; Feisst, Manuel; Olsavszky, Victor; Günther, Janine; Lorenz, Hanns-Martin; Souto-Carneiro, M Margarida; Hassel, Jessica C; Christopoulos, Petros; Leipe, Jan

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

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  • Media type: E-Article
  • Title: Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events
  • Contributor: Gente, Karolina; Diekmann, Leonore; Daniello, Lea; Will, Julia; Feisst, Manuel; Olsavszky, Victor; Günther, Janine; Lorenz, Hanns-Martin; Souto-Carneiro, M Margarida; Hassel, Jessica C; Christopoulos, Petros; Leipe, Jan
  • imprint: BMJ, 2023
  • Published in: Journal for ImmunoTherapy of Cancer
  • Language: English
  • DOI: 10.1136/jitc-2023-007557
  • ISSN: 2051-1426
  • Keywords: Cancer Research ; Pharmacology ; Oncology ; Molecular Medicine ; Immunology ; Immunology and Allergy
  • Origination:
  • Footnote:
  • Description: <jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 &gt;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&lt;0.05). R-irAE features and outcomes were independent of other baseline patient characteristics in both studied cancer entities.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>
  • Access State: Open Access