Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors

Author:

Valero CristinaORCID,Lee Mark,Hoen Douglas,Weiss Kate,Kelly Daniel W.,Adusumilli Prasad S.ORCID,Paik Paul K.,Plitas George,Ladanyi Marc,Postow Michael A.,Ariyan Charlotte E.,Shoushtari Alexander N.ORCID,Balachandran Vinod P.ORCID,Hakimi A. AriORCID,Crago Aimee M.,Long Roche Kara C.,Smith J. JoshuaORCID,Ganly Ian,Wong Richard J.,Patel Snehal G.,Shah Jatin P.ORCID,Lee Nancy Y.,Riaz NadeemORCID,Wang Jingming,Zehir AhmetORCID,Berger Michael F.,Chan Timothy A.,Seshan Venkatraman E.ORCID,Morris Luc G. T.ORCID

Abstract

AbstractTreatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types. Combining NLR with tumor mutational burden (TMB), the probability of benefit from ICI is significantly higher (OR = 3.22; 95% CI, 2.26-4.58; P < 0.001) in the NLR low/TMB high group compared to the NLR high/TMB low group. NLR is a suitable candidate for a cost-effective and widely accessible biomarker, and can be combined with TMB for additional predictive capacity.

Funder

Fundación Alfonso Martín Escudero

U.S. Department of Health & Human Services | NIH | National Cancer Institute

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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