Peripheral Blood Biomarkers Predictive of Efficacy Outcome and Immune-Related Adverse Events in Advanced Gastrointestinal Cancers Treated with Checkpoint Inhibitors

Zhang, Zhening; Xie, Tong; Qi, Changsong; Zhang, Xiaotian; Shen, Lin; Peng, Zhi

doi:10.3390/cancers14153736

Cited by 8 publications

(9 citation statements)

References 68 publications

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“…Previous treatment was described in four articles ( 15 – 18 ), one of which included previous antitumor regimens as one of the criteria when including patients ( 16 ). Six articles included only patients who received ICI monotherapy ( 15 , 16 , 19 – 22 ). The remaining studies were unrestricted, and they included patients who received ICI in combination with other antitumor treatments.…”

Section: Resultsmentioning

confidence: 99%

Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

Zhou

Du²,

Fu³

et al. 2023

Front. Immunol.

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BackgroundCancer is concerning owing to its high mortality rate. Consequently, methods of prolonging the life of patients with cancer have become the primary focus of attention research. In recent years, immune checkpoint inhibitors (ICIs) have achieved good clinical efficacy as antitumor drugs; however, their severe adverse effects have made their use challenging. In order to clarify the predictors of adverse effects, scientists have conducted a series of studies. Blood counts can potentially monitor risk factors associated with the occurrence of immune-related adverse events (irAEs). Herein, a meta-analysis was performed to clarify further the guiding significance of blood counts in the clinical setting.MethodsStudies that satisfied the inclusion criteria were obtained by searching the database. Included studies were those in which irAEs had been observed, and evidence of an association between blood counts and irAEs was reported. The included ones were evaluated for quality. In addition to sensitivity analysis and subgroup analysis, a meta-analysis was performed using the odds ratio (OR) and 95% confidence interval (CI) for each study.ResultsA total of 18 articles were included in our study. The analyses were performed separately according to different blood cell count indicators. The blood cell count metrics associated with irAEs were: absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio.ConclusionOur review and meta-analysis of studies suggest that absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio may serve as predictors of the emergence of irAEs. Given the small number of studies focusing on the relationship between patient blood cell counts and the risk of irAEs, future studies need to further explore the mechanisms of occurrence and potential associations.

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Section: Resultsmentioning

confidence: 99%

Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

Zhou

Du²,

Fu³

et al. 2023

Front. Immunol.

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“…In addition, the results varied somewhat between studies. A majority of studies suggested that both ratios were negative predictors for irAEs (neutrophil–lymphocyte ratio > 2.86 [ 48 ], ≥3 [ 42 , 49 ], ≥3.2 [ 33 ], ≥5 [ 50 ], >5.3 [ 31 ], and no specific cutoff [ 34 , 38 , 51 ]; platelet–lymphocyte ratio ≥ 180 [ 54 ], >300 [ 52 ], >534 [ 31 ], and no specific cutoff [ 38 ]). However, several studies could not confirm the negative association of both ratios with irAEs [ 29 , 33 , 35 , 36 , 37 , 40 , 46 , 47 , 51 , 52 , 53 , 54 ].…”

Section: Biomarkersmentioning

confidence: 99%

“…A majority of studies suggested that both ratios were negative predictors for irAEs (neutrophil–lymphocyte ratio > 2.86 [ 48 ], ≥3 [ 42 , 49 ], ≥3.2 [ 33 ], ≥5 [ 50 ], >5.3 [ 31 ], and no specific cutoff [ 34 , 38 , 51 ]; platelet–lymphocyte ratio ≥ 180 [ 54 ], >300 [ 52 ], >534 [ 31 ], and no specific cutoff [ 38 ]). However, several studies could not confirm the negative association of both ratios with irAEs [ 29 , 33 , 35 , 36 , 37 , 40 , 46 , 47 , 51 , 52 , 53 , 54 ]. Both raw cell counts and ratios from multiple studies suffered from the heterogeneity of the cutoffs, and the harmonization of the cutoff is necessary before this can be utilized in real-world settings.…”

Section: Biomarkersmentioning

confidence: 99%

Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

Ponvilawan,

Khan,

Subramanian

et al. 2024

Cancers

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Immune-related adverse events (irAEs) are the most common complication of immune checkpoint inhibitor (ICI) therapy. With the widespread use of ICIs in patients with solid tumors, up to 40% of the patients develop irAEs within five months of treatment, and 11% develop severe irAEs requiring interventions. A predictive test for irAEs would be a crucial tool for monitoring for complications during and after ICI therapy. We performed an extensive review of potential predictive biomarkers for irAEs in patients who received ICI therapy. Currently, only thyroid-stimulating hormone is utilized in common clinical practice. This is due to the unavailability of commercial tests and unclear predictive values from various studies. Given the lack of single strong predictive biomarkers, some novel approaches using composite scores using genomic, transcriptomics, cytokine levels, or clinical parameters appear appealing. Still, these have yet to be validated and incorporated into clinical practice. Further research conducted to validate the models before implementing them into real-world settings will be of the utmost importance for irAE prediction.

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“…Recently, there has been a growing interest in the field of peripheral blood to identify non-invasive, cost-effective, easily accessible, and promising prognostic biomarkers to predict prognostic and toxicity of ICIs [ 10 ]. Consequently, many peripheral blood inflammatory-nutritional indices such as albumin, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), and C-reactive protein-albumin ratio (CAR) were found to link with metabolic homeostasis and affect the survival outcomes of ICIs [ 11 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

New biomarkers exploration and nomogram construction of prognostic and immune-related adverse events of advanced non-small cell lung cancer patients receiving immune checkpoint inhibitors

et al. 2023

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Background Immune checkpoint inhibitors (ICIs) are regarded as the most promising treatment for advanced-stage non-small cell lung cancer (aNSCLC). Unfortunately, there has been no unified accuracy biomarkers and systematic model specifically identified for prognostic and severe immune-related adverse events (irAEs). Our goal was to discover new biomarkers and develop a publicly accessible method of identifying patients who may maximize benefit from ICIs. Methods This retrospective study enrolled 138 aNSCLC patients receiving ICIs treatment. Progression-free survival (PFS) and severe irAEs were end-points. Data of demographic features, severe irAEs, and peripheral blood inflammatory-nutritional and immune indices before and after 1 or 2 cycles of ICIs were collected. Independent factors were selected by least absolute shrinkage and selection operator (LASSO) combined with multivariate analysis, and incorporated into nomogram construction. Internal validation was performed by applying area under curve (AUC), calibration plots, and decision curve. Results Three nomograms with great predictive accuracy and discriminatory power were constructed in this study. Among them, two nomograms based on combined inflammatory-nutritional biomarkers were constructed for PFS (1 year-PFS and 2 year-PFS) and severe irAEs respectively, and one nomogram was constructed for 1 year-PFS based on immune indices. ESCLL nomogram (based on ECOG PS, preSII, changeCAR, changeLYM and postLDH) was constructed to assess PFS (1-, 2-year-AUC = 0.893 [95% CI 0.837–0.950], 0.828 [95% CI 0.721–0.935]). AdNLA nomogram (based on age, change-dNLR, changeLMR and postALI) was constructed to predict the risk of severe irAEs (AUC = 0.762 [95% CI 0.670–0.854]). NKT-B nomogram (based on change-CD3+CD56+CD16+NKT-like cells and change-B cells) was constructed to assess PFS (1-year-AUC = 0.872 [95% CI 0.764–0.965]). Although immune indices could not be modeled for severe irAEs prediction due to limited data, we were the first to find CD3+CD56+CD16+NKT-like cells were not only correlated with PFS but also associated with severe irAEs, which have not been reported in the study of aNSCLC-ICIs. Furthermore, our study also discovered higher change-CD4+/CD8+ ratio was significantly associated with severe irAEs. Conclusions These three new nomograms proceeded from non-invasive and straightforward peripheral blood data may be useful for decisions-making. CD3+CD56+CD16+NKT-like cells were first discovered to be an important biomarker for treatment and severe irAEs, and play a vital role in distinguishing the therapy response and serious toxicity of ICIs.

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Peripheral Blood Biomarkers Predictive of Efficacy Outcome and Immune-Related Adverse Events in Advanced Gastrointestinal Cancers Treated with Checkpoint Inhibitors

Cited by 8 publications

References 68 publications

Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

New biomarkers exploration and nomogram construction of prognostic and immune-related adverse events of advanced non-small cell lung cancer patients receiving immune checkpoint inhibitors

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