TY - JOUR
T1 - Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma
AU - Dharmapuri, Sirish
AU - Özbek, Umut
AU - Jethra, Hiren
AU - Jun, Tomi
AU - Marron, Thomas U
AU - Saeed, Anwaar
AU - Huang, Yi-Hsiang
AU - Muzaffar, Mahvish
AU - Pinter, Matthias
AU - Balcar, Lorenz
AU - Fulgenzi, Claudia
AU - Amara, Suneetha
AU - Weinmann, Arndt
AU - Personeni, Nicola
AU - Scheiner, Bernhard
AU - Pressiani, Tiziana
AU - Navaid, Musharraf
AU - Bengsch, Bertram
AU - Paul, Sonal
AU - Khan, Uqba
AU - Bettinger, Dominik
AU - Nishida, Naoshi
AU - Mohamed, Yehia Ibrahim
AU - Vogel, Arndt
AU - Gampa, Anuhya
AU - Korolewicz, James
AU - Cammarota, Antonella
AU - Kaseb, Ahmed
AU - Galle, Peter R
AU - Pillai, Anjana
AU - Wang, Ying-Hong
AU - Cortellini, Alessio
AU - Kudo, Masatoshi
AU - D'Alessio, Antonio
AU - Rimassa, Lorenza
AU - PINATO, David James
AU - Ang, Celina
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Immune toxicity
KW - Immunotherapy
KW - Inflammatory biomarkers
KW - Neutrophil-lymphocyte ratio
KW - Platelet-lymphocyte ratio
KW - Immune toxicity
KW - Immunotherapy
KW - Inflammatory biomarkers
KW - Neutrophil-lymphocyte ratio
KW - Platelet-lymphocyte ratio
UR - https://iris.uniupo.it/handle/11579/202243
U2 - 10.4251/wjgo.v15.i11.1900
DO - 10.4251/wjgo.v15.i11.1900
M3 - Article
SN - 1948-5204
VL - 15
JO - World Journal of Gastrointestinal Oncology
JF - World Journal of Gastrointestinal Oncology
IS - 11
ER -