Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study

Abstract

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Neutrophil–lymphocyte ratio predicts early outcomes in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: a multicenter analysis

“…Several studies have reported the relationship between NLR and immune-related adverse events in patients with malignancies treated with immune checkpoint inhibitors [36][37][38]. However, the relationship between adverse events and NLR in patients with HCC treated with Atez/Bev has not been sufficiently investigated.…”

Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases

“…An isolated rise in neutrophil count, and, consequently, an elevated NLR, can be observed in several conditions: bacterial or fungal infection [ 4 , 5 , 6 ], acute stroke [ 7 ], myocardial infarction [ 8 ], atherosclerosis [ 9 ], severe trauma [ 10 ], cancer [ 11 ], post-surgery complications [ 12 ] and any condition characterized by tissue damage that activates SIRS. This is because the early hyperdynamic phase of infection is characterized by a proinflammatory state, mediated by neutrophils and other inflammatory cells [ 4 ].…”

Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature

“…atezolizumab, durvalumab and avelumab) are now standard and effective anticancer agents serving as the backbone of cancer therapy for a wide range of cancer types (1,(4)(5)(6). However, the same enhancement of the immune response can give rise to undesirable, off-target and inflammatory immune-related adverse events (irAEs) (2,7). A range of irAEs have been described to occur in almost every organ system, ranging from mild to high grade irAEs that can be fatal (8).…”