Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved..
BACKGROUND: A well-recognized class effect of immune checkpoint inhibitors (ICI) is immune-related adverse events (IrAEs) ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI. Deaths are reported in < 5% of patients treated with ICI. There are, however, no reliable markers to predict the onset and severity of IrAEs. We tested the association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at baseline with development of clinically significant IrAEs (grade ≥ 2) in hepatocellular carcinoma (HCC) patients treated with ICI.
AIM: To test the association between NLR and PLR at baseline with development of clinically significant IrAEs (grade ≥ 2) in HCC patients treated with ICI.
METHODS: Data was extracted from an international database from a consortium of 11 tertiary-care referral centers. NLR = absolute neutrophil count/absolute lymphocyte count (ALC) and PLR = platelet count/ALC. Cutoff of 5 was used for NLR and 300 for PLR based on literature. We also tested the association between antibiotic and steroid exposure to IrAEs.
RESULTS: Data was collected from 361 patients treated between 2016-2020 across the United States (67%), Asia (14%) and Europe (19%). Most patients received Nivolumab (n = 255, 71%). One hundred sixty-seven (46%) patients developed at least one IrAE, highest grade 1 in 80 (48%), grade ≥ 2 in 87 (52%) patients. In a univariable regression model PLR > 300 was significantly associated with a lower incidence of grade ≥ 2 IrAEs (OR = 0.40; P = 0.044). Similarly, a trend was observed between NLR > 5 and lower incidence of grade ≥ 2 IrAEs (OR = 0.58; P = 0.097). Multivariate analyses confirmed PLR > 300 as an independent predictive marker of grade ≥ 2 IrAEs (OR = 0.26; P = 0.011), in addition to treatment with programmed cell death ligand 1 (PD-1)/cytotoxic T lymphocyte-associated protein-4 (OR = 2.57; P = 0.037) and PD-1/tyrosine kinase inhibitor (OR = 3.39; P = 0.01) combinations. Antibiotic use was not associated with IrAE incidence (OR = 1.02; P = 0.954). Patients treated with steroids had a > 2-fold higher incidence of grade ≥ 2 IrAEs (OR = 2.74; P < 0.001), although 74% were prescribed steroids for the treatment of IrAEs.
CONCLUSION: Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs, lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI. This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
World journal of gastrointestinal oncology - 15(2023), 11 vom: 15. Nov., Seite 1900-1912 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dharmapuri, Sirish [VerfasserIn] |
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| Links: |
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| Themen: |
Immune toxicity |
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| Anmerkungen: |
Date Revised 11.12.2023 published: Print Citation Status PubMed-not-MEDLINE |
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| doi: |
10.4251/wjgo.v15.i11.1900 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36568449X |
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| 100 | 1 | |a Dharmapuri, Sirish |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: A well-recognized class effect of immune checkpoint inhibitors (ICI) is immune-related adverse events (IrAEs) ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI. Deaths are reported in < 5% of patients treated with ICI. There are, however, no reliable markers to predict the onset and severity of IrAEs. We tested the association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at baseline with development of clinically significant IrAEs (grade ≥ 2) in hepatocellular carcinoma (HCC) patients treated with ICI | ||
| 520 | |a AIM: To test the association between NLR and PLR at baseline with development of clinically significant IrAEs (grade ≥ 2) in HCC patients treated with ICI | ||
| 520 | |a METHODS: Data was extracted from an international database from a consortium of 11 tertiary-care referral centers. NLR = absolute neutrophil count/absolute lymphocyte count (ALC) and PLR = platelet count/ALC. Cutoff of 5 was used for NLR and 300 for PLR based on literature. We also tested the association between antibiotic and steroid exposure to IrAEs | ||
| 520 | |a RESULTS: Data was collected from 361 patients treated between 2016-2020 across the United States (67%), Asia (14%) and Europe (19%). Most patients received Nivolumab (n = 255, 71%). One hundred sixty-seven (46%) patients developed at least one IrAE, highest grade 1 in 80 (48%), grade ≥ 2 in 87 (52%) patients. In a univariable regression model PLR > 300 was significantly associated with a lower incidence of grade ≥ 2 IrAEs (OR = 0.40; P = 0.044). Similarly, a trend was observed between NLR > 5 and lower incidence of grade ≥ 2 IrAEs (OR = 0.58; P = 0.097). Multivariate analyses confirmed PLR > 300 as an independent predictive marker of grade ≥ 2 IrAEs (OR = 0.26; P = 0.011), in addition to treatment with programmed cell death ligand 1 (PD-1)/cytotoxic T lymphocyte-associated protein-4 (OR = 2.57; P = 0.037) and PD-1/tyrosine kinase inhibitor (OR = 3.39; P = 0.01) combinations. Antibiotic use was not associated with IrAE incidence (OR = 1.02; P = 0.954). Patients treated with steroids had a > 2-fold higher incidence of grade ≥ 2 IrAEs (OR = 2.74; P < 0.001), although 74% were prescribed steroids for the treatment of IrAEs | ||
| 520 | |a CONCLUSION: Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs, lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI. This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Immune toxicity | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Inflammatory biomarkers | |
| 650 | 4 | |a Neutrophil-lymphocyte ratio | |
| 650 | 4 | |a Platelet-lymphocyte ratio | |
| 700 | 1 | |a Özbek, Umut |e verfasserin |4 aut | |
| 700 | 1 | |a Jethra, Hiren |e verfasserin |4 aut | |
| 700 | 1 | |a Jun, Tomi |e verfasserin |4 aut | |
| 700 | 1 | |a Marron, Thomas U |e verfasserin |4 aut | |
| 700 | 1 | |a Saeed, Anwaar |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yi-Hsiang |e verfasserin |4 aut | |
| 700 | 1 | |a Muzaffar, Mahvish |e verfasserin |4 aut | |
| 700 | 1 | |a Pinter, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Balcar, Lorenz |e verfasserin |4 aut | |
| 700 | 1 | |a Fulgenzi, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Amara, Suneetha |e verfasserin |4 aut | |
| 700 | 1 | |a Weinmann, Arndt |e verfasserin |4 aut | |
| 700 | 1 | |a Personeni, Nicola |e verfasserin |4 aut | |
| 700 | 1 | |a Scheiner, Bernhard |e verfasserin |4 aut | |
| 700 | 1 | |a Pressiani, Tiziana |e verfasserin |4 aut | |
| 700 | 1 | |a Navaid, Musharraf |e verfasserin |4 aut | |
| 700 | 1 | |a Bengsch, Bertram |e verfasserin |4 aut | |
| 700 | 1 | |a Paul, Sonal |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Uqba |e verfasserin |4 aut | |
| 700 | 1 | |a Bettinger, Dominik |e verfasserin |4 aut | |
| 700 | 1 | |a Nishida, Naoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Mohamed, Yehia Ibrahim |e verfasserin |4 aut | |
| 700 | 1 | |a Vogel, Arndt |e verfasserin |4 aut | |
| 700 | 1 | |a Gampa, Anuhya |e verfasserin |4 aut | |
| 700 | 1 | |a Korolewicz, James |e verfasserin |4 aut | |
| 700 | 1 | |a Cammarota, Antonella |e verfasserin |4 aut | |
| 700 | 1 | |a Kaseb, Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Galle, Peter R |e verfasserin |4 aut | |
| 700 | 1 | |a Pillai, Anjana |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ying-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Cortellini, Alessio |e verfasserin |4 aut | |
| 700 | 1 | |a Kudo, Masatoshi |e verfasserin |4 aut | |
| 700 | 1 | |a D'Alessio, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Rimassa, Lorenza |e verfasserin |4 aut | |
| 700 | 1 | |a Pinato, David James |e verfasserin |4 aut | |
| 700 | 1 | |a Ang, Celina |e verfasserin |4 aut | |
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