Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis
BackgroundIn recent years, immune checkpoint inhibitors (ICIs) have shown significant efficacy in treating various malignancies and have become a key therapeutic approach in cancer treatment. However, while ICIs activate the immune system, they can also induce immune-related adverse events (irAEs)....
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528084/full |
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| author | Xinyu Zhang Bei Zhang Danfei Li Yunchao Yang Sen Lin Ruiqi Zhao Yijia Li Lisheng Peng |
| author_facet | Xinyu Zhang Bei Zhang Danfei Li Yunchao Yang Sen Lin Ruiqi Zhao Yijia Li Lisheng Peng |
| author_sort | Xinyu Zhang |
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| description | BackgroundIn recent years, immune checkpoint inhibitors (ICIs) have shown significant efficacy in treating various malignancies and have become a key therapeutic approach in cancer treatment. However, while ICIs activate the immune system, they can also induce immune-related adverse events (irAEs). Due to the variability in the frequency and severity of irAEs, clinical management faces a significant challenge in balancing antitumor efficacy with the risk of irAEs. Predicting and preventing irAEs during the early stages of treatment has become a critical research focus in cancer immunotherapy. This study aims to evaluate the predictive value of peripheral blood cell counts for irAEs.MethodsStudies meeting the inclusion criteria were identified through database searches. The standardized mean difference (SMD) was used to compare continuous blood cell counts. For studies that did not provide adjusted odds ratios (ORs) and 95% confidence intervals (CIs), crude ORs for categorized blood cell counts were calculated. The study protocol was registered on PROSPERO (CRD42024592126).ResultsThe meta-analysis included 60 studies involving 16,736 cancer patients treated with ICIs. Compared to patients without irAEs, those experiencing irAEs had significantly higher baseline continuous ALC (SMD = 0.12, 95% CI = 0.01-0.24), while ANC (SMD = -0.18, 95% CI = -0.28 to -0.07) and PLR (SMD = -0.32, 95% CI = -0.60 to -0.04) were significantly lower. Similarly, categorized blood cell counts indicated that higher baseline ALC (OR = 2.46, 95% CI = 1.69-3.57) and AEC (OR = 2.05, 95% CI = 1.09-3.85), along with lower baseline NLR (OR = 0.64, 95% CI = 0.50-0.81) and PLR (OR = 0.63, 95% CI = 0.48-0.82), were associated with an increased risk of irAEs. Subgroup analysis further identified cutoff values for ALC (2×10^9/L), NLR (5 or 3), and PLR (180) as better predictors of irAEs.ConclusionHigher baseline ALC and AEC, along with lower baseline ANC, NLR, and PLR, are associated with an increased risk of irAEs. However, further research is needed to determine the optimal cutoff values and to explore the efficacy of blood cell counts in predicting specific types of irAEs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024592126. |
| format | Article |
| id | doaj-art-f2d7d9c666784a6b9deeb9ab00385e97 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-f2d7d9c666784a6b9deeb9ab00385e972025-01-30T06:22:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15280841528084Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysisXinyu Zhang0Bei Zhang1Danfei Li2Yunchao Yang3Sen Lin4Ruiqi Zhao5Yijia Li6Lisheng Peng7The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaThe Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaThe Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaShandong College of Traditional Chinese Medicine, Shandong, Yantai, ChinaThe Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaThe Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaThe Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, ChinaDepartment of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, ChinaBackgroundIn recent years, immune checkpoint inhibitors (ICIs) have shown significant efficacy in treating various malignancies and have become a key therapeutic approach in cancer treatment. However, while ICIs activate the immune system, they can also induce immune-related adverse events (irAEs). Due to the variability in the frequency and severity of irAEs, clinical management faces a significant challenge in balancing antitumor efficacy with the risk of irAEs. Predicting and preventing irAEs during the early stages of treatment has become a critical research focus in cancer immunotherapy. This study aims to evaluate the predictive value of peripheral blood cell counts for irAEs.MethodsStudies meeting the inclusion criteria were identified through database searches. The standardized mean difference (SMD) was used to compare continuous blood cell counts. For studies that did not provide adjusted odds ratios (ORs) and 95% confidence intervals (CIs), crude ORs for categorized blood cell counts were calculated. The study protocol was registered on PROSPERO (CRD42024592126).ResultsThe meta-analysis included 60 studies involving 16,736 cancer patients treated with ICIs. Compared to patients without irAEs, those experiencing irAEs had significantly higher baseline continuous ALC (SMD = 0.12, 95% CI = 0.01-0.24), while ANC (SMD = -0.18, 95% CI = -0.28 to -0.07) and PLR (SMD = -0.32, 95% CI = -0.60 to -0.04) were significantly lower. Similarly, categorized blood cell counts indicated that higher baseline ALC (OR = 2.46, 95% CI = 1.69-3.57) and AEC (OR = 2.05, 95% CI = 1.09-3.85), along with lower baseline NLR (OR = 0.64, 95% CI = 0.50-0.81) and PLR (OR = 0.63, 95% CI = 0.48-0.82), were associated with an increased risk of irAEs. Subgroup analysis further identified cutoff values for ALC (2×10^9/L), NLR (5 or 3), and PLR (180) as better predictors of irAEs.ConclusionHigher baseline ALC and AEC, along with lower baseline ANC, NLR, and PLR, are associated with an increased risk of irAEs. However, further research is needed to determine the optimal cutoff values and to explore the efficacy of blood cell counts in predicting specific types of irAEs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024592126.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528084/fullimmune checkpoint inhibitorsimmunotherapyimmune-related adverse eventsblood cell countbiomarkerrisk factor |
| spellingShingle | Xinyu Zhang Bei Zhang Danfei Li Yunchao Yang Sen Lin Ruiqi Zhao Yijia Li Lisheng Peng Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis Frontiers in Immunology immune checkpoint inhibitors immunotherapy immune-related adverse events blood cell count biomarker risk factor |
| title | Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis |
| title_full | Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis |
| title_fullStr | Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis |
| title_full_unstemmed | Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis |
| title_short | Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis |
| title_sort | peripheral blood cell counts as predictors of immune related adverse events in cancer patients receiving immune checkpoint inhibitors a systematic review and meta analysis |
| topic | immune checkpoint inhibitors immunotherapy immune-related adverse events blood cell count biomarker risk factor |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528084/full |
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