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.


Journal

Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310

Informations de publication

Date de publication:
06 2023
Historique:
revised: 24 03 2023
received: 31 08 2022
accepted: 27 03 2023
medline: 20 6 2023
pubmed: 21 4 2023
entrez: 21 04 2023
Statut: ppublish

Résumé

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. 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. 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 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.

Sections du résumé

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
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.

Identifiants

pubmed: 37084178
doi: 10.1002/cam4.5919
pmc: PMC10278511
doi:

Substances chimiques

C-Reactive Protein 9007-41-4

Types de publication

Observational Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

12253-12262

Informations de copyright

© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Références

Oncoimmunology. 2017 Nov 13;7(2):e1393134
pubmed: 29308325
Clin Cancer Res. 2016 Nov 15;22(22):5487-5496
pubmed: 27185375
J Immunother Cancer. 2019 Nov 15;7(1):306
pubmed: 31730012
Immunotherapy. 2017 Jan;9(2):115-121
pubmed: 28128709
J Cancer Res Clin Oncol. 2019 Feb;145(2):511-521
pubmed: 30539281
Nat Rev Clin Oncol. 2019 Sep;16(9):563-580
pubmed: 31092901
Nat Med. 2002 Aug;8(8):793-800
pubmed: 12091876
Clin Cancer Res. 2016 Jun 15;22(12):2908-18
pubmed: 26787752
Front Med (Lausanne). 2019 May 29;6:119
pubmed: 31192215
ESMO Open. 2019 Aug 16;4(4):e000531
pubmed: 31555483
Curr Oncol. 2018 Oct;25(5):e403-e410
pubmed: 30464691
J Clin Oncol. 2010 Jul 1;28(19):3167-75
pubmed: 20516446
J Clin Oncol. 2015 Oct 1;33(28):3193-8
pubmed: 26282644
Melanoma Res. 2021 Aug 1;31(4):371-377
pubmed: 34054056
Oncologist. 2020 May;25(5):438-446
pubmed: 32048768
N Engl J Med. 2010 Aug 19;363(8):711-23
pubmed: 20525992
Cancer Immunol Immunother. 2014 Jul;63(7):675-83
pubmed: 24695951
Lung Cancer. 2020 Dec;150:76-82
pubmed: 33080551
Cancer Med. 2023 Jun;12(11):12253-12262
pubmed: 37084178
JAMA Oncol. 2018 Mar 01;4(3):374-378
pubmed: 28975219
Cancers (Basel). 2020 Aug 17;12(8):
pubmed: 32824580
J Clin Oncol. 2017 Mar;35(7):785-792
pubmed: 28068177
Lung Cancer. 2018 Jan;115:71-74
pubmed: 29290265
PLoS One. 2015 Dec 30;10(12):e0143080
pubmed: 26717416
J Cancer Res Clin Oncol. 2019 Feb;145(2):479-485
pubmed: 30506406
J Immunother Cancer. 2020 Jun;8(1):
pubmed: 32581042
Clin Lung Cancer. 2019 May;20(3):201-207
pubmed: 30442524
J Immunother Cancer. 2019 Apr 3;7(1):99
pubmed: 30944023
Nat Commun. 2020 Oct 2;11(1):4946
pubmed: 33009409
Sci Rep. 2022 Jan 25;12(1):1294
pubmed: 35079086
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
J Transl Med. 2014 May 07;12:116
pubmed: 24885479
Acta Oncol. 2018 Jun;57(6):867-872
pubmed: 29241410
J Clin Oncol. 2012 Jul 20;30(21):2691-7
pubmed: 22614989
Curr Cardiol Rep. 2021 Jul 1;23(8):98
pubmed: 34196833
Oncologist. 2020 Aug;25(8):669-679
pubmed: 31943525

Auteurs

Tarun Mehra (T)

Department of Oncology, Medical University Clinic, Kantonsspital Baselland, Liestal, Switzerland.
Department of Oncology & Hematology, University Hospital Zürich, University of Zurich, Zürich, Switzerland.

Kanchan Dongre (K)

Department of Clinical Pharmacology & Toxicology, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Patient Safety, University Hospital Basel, Basel, Switzerland.

Maria Boesing (M)

Medical University Clinic, Kantonsspital Baselland, Liestal, Switzerland.

Patricia Frei (P)

Department of Clinical Pharmacology & Toxicology, University Hospital Basel, University of Basel, Basel, Switzerland.

Claudia Suenderhauf (C)

Department of Clinical Pharmacology & Toxicology, University Hospital Basel, University of Basel, Basel, Switzerland.

Alfred Zippelius (A)

Department of Oncology, University Hospital Basel, University of Basel, Basel, Switzerland.

Joerg D Leuppi (JD)

Medical University Clinic, Kantonsspital Baselland, Liestal, Switzerland.

Andreas Wicki (A)

Department of Oncology, Medical University Clinic, Kantonsspital Baselland, Liestal, Switzerland.
Department of Oncology & Hematology, University Hospital Zürich, University of Zurich, Zürich, Switzerland.

Anne B Leuppi-Taegtmeyer (AB)

Department of Clinical Pharmacology & Toxicology, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Patient Safety, University Hospital Basel, Basel, Switzerland.
Medical University Clinic, Kantonsspital Baselland, Liestal, Switzerland.

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