Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors
Cristina Valero, Mark Lee, Douglas R. Hoen, Kate Weiss, Daniel W. Kelly, Prasad S. Adusumilli, Paul K. Paik, George Plitas, Marc Ladanyi, Michael A. Postow, Charlotte E. Ariyan, Alexander N. Shoushtari, Vinod P. Balachandran, A. Ari Hakimi, Aimeé M. Crago, Kara Long Roche, J. Joshua Smith, Ian Ganly, Richard J. Wong, Snehal G. Patel, Jatin P. Shah, Nancy Y. Lee, Nadeem Riaz, Jingming Wang, Ahmet Zehir, Michael F. Berger, Timothy A. Chan, Venkatraman Seshan, Luc G.T. Morris
Abstract
Treatment 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.