Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events

Objective: We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events (irAEs) as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors (ICIs) in patients with advanced pan-cancer in a real-world setti...

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Autores principales:	Rilan Bai, Naifei Chen, Xiao Chen, Lingyu Li, Wei Song, Wei Li, Yuguang Zhao, Yongfei Zhang, Fujun Han, Zheng Lyu, Jiuwei Cui
Formato:	article
Lenguaje:	EN
Publicado:	China Anti-Cancer Association 2021
Materias:	neoplasm immune checkpoint inhibitors immune-related adverse events predictor efficacy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0219a785d3ca4aa8a63500ce7e7e6f43
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spelling	oai:doaj.org-article:0219a785d3ca4aa8a63500ce7e7e6f432021-11-30T11:27:44ZAnalysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events2095-394110.20892/j.issn.2095-3941.2021.0052https://doaj.org/article/0219a785d3ca4aa8a63500ce7e7e6f432021-11-01T00:00:00Zhttp://www.cancerbiomed.org/index.php/cocr/article/view/1981https://doaj.org/toc/2095-3941Objective: We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events (irAEs) as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors (ICIs) in patients with advanced pan-cancer in a real-world setting. Methods: We retrospectively analyzed data from 105 patients with advanced pan-cancer treated with multi-type ICIs at the First Hospital of Jilin University between January 1, 2016 and August 1, 2020. We used logistic regression analyses to investigate the associations of irAEs with clinical baseline characteristics, blood count parameters, and biochemical indicators during treatment. Receiver operating characteristic curves were used to determine cutoff values for parameters and area under the curve values. Kaplan–Meier and Cox multivariate regression analyses were performed to estimate the relationships of baseline characteristics and irAEs with progression-free survival (PFS) and overall survival (OS). Results: A lower relative lymphocyte count (cutoff = 28.5%), higher albumin level (cutoff = 39.05 g/L), and higher absolute eosinophil count (AEC) (cutoff = 0.175 × 109/L) were significantly associated with the occurrence of irAEs, among which a higher AEC (cutoff = 0.205 × 109/L) was strongly associated with skin-related irAEs [odds ratios (ORs) = 0.163, P = 0.004]. Moreover, a higher lactate dehydrogenase level (cutoff = 237.5 U/L) was an independent predictor of irAEs of grade ≥ 3 (OR = 0.083, P = 0.023). In immune cell subgroup analysis, a lower absolute count of CD8+CD28− suppressor T cells (OR = 0.806; 95% confidence interval: 0.643–1.011; P = 0.062), which are regulatory T lymphocytes, was associated with the occurrence of irAEs, although the difference was not statistically significant. Furthermore, a higher percentage of CD19+ B cells was associated with the occurrence of irAEs of grade ≥ 3 (P = 0.02) and grade ≥ 2 (P = 0.051). In addition, patients with any grade of irAE had a significantly high PFS (8.37 vs. 3.77 months, hazard ratios (HR) = 2.02, P = 0.0038) and OS (24.77 vs. 13.83 months, HR = 1.84; P = 0.024). Conclusions: This retrospective study reports clinical profile data for irAEs in unselected patients in a real-world setting and explored some parameters that may be potential predictive markers of the occurrence, type, or grade of irAEs in clinical practice. Evidence of a correlation between safety and efficacy may facilitate a complete assessment of the risk-benefit ratio for patients treated with ICIs.Rilan BaiNaifei ChenXiao ChenLingyu LiWei SongWei LiYuguang ZhaoYongfei ZhangFujun HanZheng LyuJiuwei CuiChina Anti-Cancer Associationarticleneoplasmimmune checkpoint inhibitorsimmune-related adverse eventspredictorefficacyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Biology & Medicine, Vol 18, Iss 4, Pp 1118-1133 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neoplasm immune checkpoint inhibitors immune-related adverse events predictor efficacy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	neoplasm immune checkpoint inhibitors immune-related adverse events predictor efficacy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Rilan Bai Naifei Chen Xiao Chen Lingyu Li Wei Song Wei Li Yuguang Zhao Yongfei Zhang Fujun Han Zheng Lyu Jiuwei Cui Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events
description	Objective: We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events (irAEs) as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors (ICIs) in patients with advanced pan-cancer in a real-world setting. Methods: We retrospectively analyzed data from 105 patients with advanced pan-cancer treated with multi-type ICIs at the First Hospital of Jilin University between January 1, 2016 and August 1, 2020. We used logistic regression analyses to investigate the associations of irAEs with clinical baseline characteristics, blood count parameters, and biochemical indicators during treatment. Receiver operating characteristic curves were used to determine cutoff values for parameters and area under the curve values. Kaplan–Meier and Cox multivariate regression analyses were performed to estimate the relationships of baseline characteristics and irAEs with progression-free survival (PFS) and overall survival (OS). Results: A lower relative lymphocyte count (cutoff = 28.5%), higher albumin level (cutoff = 39.05 g/L), and higher absolute eosinophil count (AEC) (cutoff = 0.175 × 109/L) were significantly associated with the occurrence of irAEs, among which a higher AEC (cutoff = 0.205 × 109/L) was strongly associated with skin-related irAEs [odds ratios (ORs) = 0.163, P = 0.004]. Moreover, a higher lactate dehydrogenase level (cutoff = 237.5 U/L) was an independent predictor of irAEs of grade ≥ 3 (OR = 0.083, P = 0.023). In immune cell subgroup analysis, a lower absolute count of CD8+CD28− suppressor T cells (OR = 0.806; 95% confidence interval: 0.643–1.011; P = 0.062), which are regulatory T lymphocytes, was associated with the occurrence of irAEs, although the difference was not statistically significant. Furthermore, a higher percentage of CD19+ B cells was associated with the occurrence of irAEs of grade ≥ 3 (P = 0.02) and grade ≥ 2 (P = 0.051). In addition, patients with any grade of irAE had a significantly high PFS (8.37 vs. 3.77 months, hazard ratios (HR) = 2.02, P = 0.0038) and OS (24.77 vs. 13.83 months, HR = 1.84; P = 0.024). Conclusions: This retrospective study reports clinical profile data for irAEs in unselected patients in a real-world setting and explored some parameters that may be potential predictive markers of the occurrence, type, or grade of irAEs in clinical practice. Evidence of a correlation between safety and efficacy may facilitate a complete assessment of the risk-benefit ratio for patients treated with ICIs.
format	article
author	Rilan Bai Naifei Chen Xiao Chen Lingyu Li Wei Song Wei Li Yuguang Zhao Yongfei Zhang Fujun Han Zheng Lyu Jiuwei Cui
author_facet	Rilan Bai Naifei Chen Xiao Chen Lingyu Li Wei Song Wei Li Yuguang Zhao Yongfei Zhang Fujun Han Zheng Lyu Jiuwei Cui
author_sort	Rilan Bai
title	Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events
title_short	Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events
title_full	Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events
title_fullStr	Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events
title_full_unstemmed	Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events
title_sort	analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events
publisher	China Anti-Cancer Association
publishDate	2021
url	https://doaj.org/article/0219a785d3ca4aa8a63500ce7e7e6f43
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Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events

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