Neutrophil-to-lymphocyte ratio as a predictive biomarker for hyperprogressive disease mediated by immune checkpoint inhibitors: a systematic review and meta-analysis

Background: Hyperprogressive disease (HPD) is a novel pattern of paradoxically rapid tumor progression, which often leads to early death, mostly in the first 2 months of treatment with immune checkpoint inhibitors (ICIs). Currently, there is no validated biomarker to assess patients at risk of HPD.

Aim: The aim of this study was to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in HPD and establish a reliable variable to support clinicians in defining personalized treatment strategies.

Methods: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched for studies published before 31 December 2023. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects or a fixed-effects model to evaluate the association between the NLR and the risk of HPD.

Results: A total of 17 studies with 2,964 patients were included for meta-analysis. The incidence of HPD across different types of tumors ranged from 6.3% to 35.6%. In the pooled analysis of the NLR and HPD, we identified that the NLR significantly associated with the risk of HPD (OR = 0.65; 95% CI: 0.46 to 0.91; p = 0.01) (I ² = 52%, p = 0.007).

Conclusion: In the future, the NLR may serve as a remarkable biomarker for predicting the risk of HPD in clinical practice.