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Predictive value of NLR and PLR for immune-related adverse events: a systematic review and meta-analysis

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Abstract

Background

Currently, there is a lack of affordable and accessible indicators that can accurately predict immune-related adverse events (irAEs) resulting from the use of immune checkpoint inhibitors (ICIs). In order to address this knowledge gap, our study explore the potential predictive value of two ratios, namely the neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), for irAEs in cancer patients.

Methods

A systematic search was performed in PubMed, Embase, and the Cochrane library. Studies involving NLR or PLR with irAEs were included. Quality and risk of bias of the selected studies were assessed. Forest plots were created based on Cox model analysis. Random effects meta-analyses were conducted to estimate odds ratio (OR) and its 95% confidence interval (CI).

Results

After screening 594 studies, a total of 7 eligible studies with 1068 cancer patients were included. Analysis based on Cox regression showed that low neutrophil–lymphocyte ratio (L-NLR) (OR = 3.02, 95% CI 1.51 to 6.05, P = 0.002) and low platelet-lymphocyte ratio (L-PLR) (OR = 1.83, 95% CI 1.21 to 2.76, P = 0.004) were associated with irAEs. In the subgroup analysis of cut-off value, when the NLR cut-off value was 3, irAEs was significantly correlated with NLR (OR = 2.63, 95% CI 1.63 to 4.26, P < 0.001).

Conclusions

Both L-NLR and L-PLR have been found to be significantly associated with irAEs. Consequently, patients identified as being at a higher risk for irAEs should be subjected to more diligent monitoring and close observation.

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Data availability

Data will be shared upon reasonable request.

Abbreviations

CI:

Confidence interval

CTLA-4:

Cytotoxic T lymphocyte-associated protein 4

H-NLR:

High neutrophil–lymphocyte ratio

H-PLR:

High platelet-lymphocyte ratio

ICIs:

Immune checkpoint inhibitors

irAEs:

Immune-related adverse events

L-NLR:

Low neutrophil–lymphocyte ratio

L-PLR:

Low platelet-lymphocyte ratio

NLR:

Neutrophil–lymphocyte ratio

NOS:

Newcastle–Ottawa Scale

NSCLC:

Non-small cell lung cancer

OR:

Odds ratio

PD-1:

Programmed cell death 1

PD-L1:

Programmed cell death ligand 1

PLR:

Platelet-lymphocyte ratio

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Funding

This study was supported by grants from Zhejiang Provincial Nature Fund Key Project (LZ23H160007) and Zhejiang Provincial Medical and Pharmaceutical Health Key Project (WKJ-ZJ-2325). 

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Author notes

  1. Hong-Rui Lu and Peng-Fei Zhu contributed equally to the work.

Authors and Affiliations

  1. Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233000, Anhui Province, China

    Hong-Rui Lu, Peng-Fei Zhu & Liu Yang

  2. Cancer Center, Department of Medical Oncology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, 310014, Zhejiang, China

    Hong-Rui Lu, Peng-Fei Zhu, Ya-Ya Deng, Zhe-Ling Chen & Liu Yang

  3. Graduate Department, Jinzhou Medical University, Jinzhou, 121000, Liaoning, China

    Ya-Ya Deng & Liu Yang

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Contributions

H-RL and P-FZ: contributed equally to this work; Z-LC, and LY: revised the manuscript. All authors wrote and revised the manuscript and issued the final approval for the version to be submitted.

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Correspondence to Zhe-Ling Chen or Liu Yang.

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12094_2023_3313_MOESM1_ESM.xlsx

Supplementary file1 Supplementary Table 1 Grade and subtype of occurrence of irAEs in the included literature. (XLSX 15 KB)

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Lu, HR., Zhu, PF., Deng, YY. et al. Predictive value of NLR and PLR for immune-related adverse events: a systematic review and meta-analysis. Clin Transl Oncol 26, 1106–1116 (2024). https://doi.org/10.1007/s12094-023-03313-3

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