Neutrophil to Lymphocyte Ratio As a Predictor for Immune-related Adverse Events in Cancer Patients Treated with Immune Checkpoint Inhibitors: a Systematic Review and Meta-analysis

Background: The use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in immune-related adverse events (irAEs), which can cause treatment discontinuation and even fatal reactions. The purpose of this study was to evaluate the usefulness of the peripheral biomarker neutrophil to lymphocyte ratio (NLR) in predicting irAEs.

Methods: A systematic search of databases was conducted to identify studies on the predictive value of NLR for irAEs. The standardized mean difference (SMD) was used to compare continuous NLR, while crude odds ratios (ORs) were calculated for categorized NLR if adjusted ORs and 95% confidence intervals (CIs) were not provided in the original study.

Results: The meta-analysis included 47 studies with a total of 11,491 cancer patients treated with ICIs. The baseline continuous NLR was significantly lower in patients with irAEs compared to those without (SMD=-1.55, 95%CI=-2.64 to -0.46, P=0.006). Similarly, categorized NLR showed that lower baseline NLR was associated with increased irAEs (OR=0.55, 95%CI=0.41-0.73, P<0.001). Subgroup analysis revealed that the OR for predicting irAEs with NLR cut-off values of 3 and 5 was 0.4 and 0.59, respectively. Interestingly, increased baseline NLR was associated with a higher incidence of immune-related liver injury (OR=2.44, 95%CI=1.23-4.84, I2 = 0%, P=0.010).

Conclusion: Our study suggests that lower baseline NLR is associated with a higher risk of overall irAEs. However, further studies are needed to determine the best cut-off value and explore the efficacy of NLR in predicting specific types of irAEs.