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Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities

BACKGROUND: The development of immune‐related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre‐treatment parameters on outcome in a large, real‐life patient cohort. METHODS:...

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Autores principales: Mehra, Tarun, Dongre, Kanchan, Boesing, Maria, Frei, Patricia, Suenderhauf, Claudia, Zippelius, Alfred, Leuppi, Joerg D., Wicki, Andreas, Leuppi‐Taegtmeyer, Anne B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278511/
https://www.ncbi.nlm.nih.gov/pubmed/37084178
http://dx.doi.org/10.1002/cam4.5919
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author Mehra, Tarun
Dongre, Kanchan
Boesing, Maria
Frei, Patricia
Suenderhauf, Claudia
Zippelius, Alfred
Leuppi, Joerg D.
Wicki, Andreas
Leuppi‐Taegtmeyer, Anne B.
author_facet Mehra, Tarun
Dongre, Kanchan
Boesing, Maria
Frei, Patricia
Suenderhauf, Claudia
Zippelius, Alfred
Leuppi, Joerg D.
Wicki, Andreas
Leuppi‐Taegtmeyer, Anne B.
author_sort Mehra, Tarun
collection PubMed
description BACKGROUND: The development of immune‐related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre‐treatment parameters on outcome in a large, real‐life patient cohort. METHODS: We performed a single‐centre, retrospective, observational study including patients who received CPIs from 2011 to 2018 and followed until 2021. The primary outcome was overall survival, and the secondary outcome was the development of irAEs. RESULTS: In total, 229 patients with different tumour entities (41% non‐small cell lung cancer [NSCLC], 29% melanoma) received a total of 282 CPI treatment courses (ipilimumab, nivolumab, pembrolizumab or atezolizumab). Thirty‐four percent of patients developed irAEs (of these 17% had CTCAE Grade ≥3). Factors independently associated with mortality were pre‐treatment CRP ≥10 mg/L (hazard ratio [HR] 2.064, p = 0.0003), comorbidity measured by Charlson comorbidity index (HR 1.149, p = 0.014) and irAEs (HR 0.644, p = 0.036) (age‐adjusted, n = 216). Baseline eosinophil count ≤0.2 × 10(9)/L was a further independent predictor of mortality (age‐, CRP‐, CCI‐ and irAE‐adjusted HR = 2.252, p = 0.002, n = 166). Anti‐CTLA‐4 use (p < 0.001), and pre‐treatment CRP <10 mg/L were independently associated with irAE occurrence (p = 0.037). CONCLUSIONS: We found an independent association between irAE occurrence and improved overall survival in a real‐life cohort spanning multiple tumour entities and treatment regimens. Pre‐treatment comorbidities, CRP and eosinophil count represent potential markers for predicting treatment response.
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spelling pubmed-102785112023-06-20 Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities Mehra, Tarun Dongre, Kanchan Boesing, Maria Frei, Patricia Suenderhauf, Claudia Zippelius, Alfred Leuppi, Joerg D. Wicki, Andreas Leuppi‐Taegtmeyer, Anne B. Cancer Med RESEARCH ARTICLES BACKGROUND: The development of immune‐related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre‐treatment parameters on outcome in a large, real‐life patient cohort. METHODS: We performed a single‐centre, retrospective, observational study including patients who received CPIs from 2011 to 2018 and followed until 2021. The primary outcome was overall survival, and the secondary outcome was the development of irAEs. RESULTS: In total, 229 patients with different tumour entities (41% non‐small cell lung cancer [NSCLC], 29% melanoma) received a total of 282 CPI treatment courses (ipilimumab, nivolumab, pembrolizumab or atezolizumab). Thirty‐four percent of patients developed irAEs (of these 17% had CTCAE Grade ≥3). Factors independently associated with mortality were pre‐treatment CRP ≥10 mg/L (hazard ratio [HR] 2.064, p = 0.0003), comorbidity measured by Charlson comorbidity index (HR 1.149, p = 0.014) and irAEs (HR 0.644, p = 0.036) (age‐adjusted, n = 216). Baseline eosinophil count ≤0.2 × 10(9)/L was a further independent predictor of mortality (age‐, CRP‐, CCI‐ and irAE‐adjusted HR = 2.252, p = 0.002, n = 166). Anti‐CTLA‐4 use (p < 0.001), and pre‐treatment CRP <10 mg/L were independently associated with irAE occurrence (p = 0.037). CONCLUSIONS: We found an independent association between irAE occurrence and improved overall survival in a real‐life cohort spanning multiple tumour entities and treatment regimens. Pre‐treatment comorbidities, CRP and eosinophil count represent potential markers for predicting treatment response. John Wiley and Sons Inc. 2023-04-21 /pmc/articles/PMC10278511/ /pubmed/37084178 http://dx.doi.org/10.1002/cam4.5919 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Mehra, Tarun
Dongre, Kanchan
Boesing, Maria
Frei, Patricia
Suenderhauf, Claudia
Zippelius, Alfred
Leuppi, Joerg D.
Wicki, Andreas
Leuppi‐Taegtmeyer, Anne B.
Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
title Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
title_full Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
title_fullStr Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
title_full_unstemmed Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
title_short Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
title_sort pre‐treatment comorbidities, c‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278511/
https://www.ncbi.nlm.nih.gov/pubmed/37084178
http://dx.doi.org/10.1002/cam4.5919
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