Xinyu Zhang, Bei Zhang, Danfei Li, Yunchao Yang, Sen Lin, Ruiqi Zhao, Yijia Li, Lisheng Peng
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This study aims to evaluate the predictive value of peripheral blood cell counts for irAEs.</p><p><strong>Methods: </strong>Studies 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).</p><p><strong>Results: </strong>The 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.</p><p><strong>Conclusion: </strong>Higher baseline ALC and AEC, along with lower baseline ANC, NLR, and PLR, are associated with an increased risk of irAEs. 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引用次数: 0
摘要
背景：近年来，免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）在治疗多种恶性肿瘤中显示出显著的疗效，已成为肿瘤治疗的重要手段。然而，在ICIs激活免疫系统的同时，它们也会诱发免疫相关不良事件（irAEs）。由于irAEs发生频率和严重程度的差异，临床管理在平衡抗肿瘤疗效和irAEs风险方面面临着重大挑战。在治疗的早期阶段预测和预防irae已成为癌症免疫治疗的一个重要研究热点。本研究旨在评估外周血细胞计数对irAEs的预测价值。方法：通过数据库检索确定符合纳入标准的研究。标准化平均差（SMD）用于比较连续血细胞计数。对于没有提供校正优势比（or）和95%置信区间（ci）的研究，计算分类血细胞计数的粗or。研究方案已在PROSPERO上注册（CRD42024592126）。结果：荟萃分析包括60项研究，涉及16736名接受ICIs治疗的癌症患者。与未发生irAEs的患者相比，经历irAEs的患者基线连续ALC （SMD = 0.12, 95% CI = 0.01-0.24）显著较高，而ANC （SMD = -0.18, 95% CI = -0.28至-0.07）和PLR （SMD = -0.32, 95% CI = -0.60至-0.04）显著较低。同样，分类血细胞计数表明，较高的基线ALC （OR = 2.46, 95% CI = 1.69-3.57）和AEC (OR = 2.05, 95% CI = 1.09-3.85)，以及较低的基线NLR （OR = 0.64, 95% CI = 0.50-0.81）和PLR （OR = 0.63, 95% CI = 0.48-0.82）与irae风险增加相关。亚组分析进一步确定了ALC （2×10^9/L）、NLR（5或3）和PLR（180）的临界值是更好的irae预测因子。结论：较高的基线ALC和AEC，以及较低的基线ANC、NLR和PLR与irae的风险增加相关。然而，需要进一步的研究来确定最佳临界值，并探索血细胞计数在预测特定类型的irae中的功效。系统综述注册：https://www.crd.york.ac.uk/PROSPERO/，标识符CRD42024592126。
Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.
Background: In 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.
Methods: Studies 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).
Results: The 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.
Conclusion: Higher 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.
期刊介绍：
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.
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