Change in neutrophil to lymphocyte ratio (NLR) as a predictor of treatment failure in renal cell carcinoma patients: Analysis of the IROC (Investigating RCC Outcomes) cohort.

Abstract

344 Background: IROC is an expanding multi-institution collaborative database which includes socioeconomic, genomic, pathologic, clinical and laboratory data in metastatic RCC patients (pts), primarily in the modern setting. Elevated baseline NLR is now an established poor prognostic factor in renal cell carcinoma (RCC) but currently has limited practical use. We hypothesized that an increase in NLR of 3 or more (NLR Failure) at 2 months on therapy could be a predictor of eventual treatment failure and shorter overall survival and thus augment the utility of this marker. Methods: Patients with complete data on NLR at time = 0 and +2 months of therapy were analyzed. Information on comorbidities, previous therapy, demographics were collected for adjusted analysis. NLR failure was defined as an increase of 3 or more compared to baseline NLR. Cox proportional hazard models were used to analyze the risk of progression and death with NLR failure at 2 months (+/- 2 weeks). Kaplan Meier graphs were constructed to trace survival functions for PFS and OS by NLR. Results: Among 165 pts; 121 were eligible (Table). NLR failure at 2 months was associated with a highly statistically significant increase in the risk of death in < 1 year (HR 6.82, 95% CI [3.16-14.70], p<0.001). In a model adjusted for NLR change, the value of baseline NLR to predict OS <1 year was non-significant (HR 1.02, p = 0.65). Similarly, NLR failure increased the risk of treatment failure in less than 6 months (HR 4.83 95% CI [ 2.29-10 .19], p<0.001), while baseline NLR did not predict it (HR 1.03, p = 0.34). These findings were unaffected by immunotherapy vs TKI therapy. NLR failure at 2 months had a 78% (11/14) positive predictive value for survival <1 year and 86% (12/14) [p=.0001] for treatment failure in 6 months. Conclusions: In this multi-institutional cohort of RCC pts; an increase in NLR of 3 or more at 2 months following therapy start predicts for an increasing risk of death and impending treatment failure with a high PPV. The prognostic value of baseline NLR is non-significant when adjusting for NLR change. NLR failure should be validated in prospective studies and could have clinical utility in management of RCC pts. [Table: see text]

Second-Line Treatment of Metastatic Renal Cell Carcinoma in the Era of Predictive Biomarkers

“…Firstly, we determined the median NLR value for the patients initiating second-line therapy, which was 2.85 ± 2.05. The findings align with the literature, where NLR values between 1.7 and 5 have been reported, with an NLR of 3 being frequently used [51][52][53]. Secondly, using ROC analysis, we identified the optimal NLR cut-off value of 3.…”

The Frontline Immunotherapy-Based Treatment of Advanced Clear Cell Renal Cell Carcinoma: Current Evidence and Clinical Perspective

“…In addition to the above, there have been many studies on biomarkers of RCC, including PBRM1 mutation [ 29 , 59 , 61 , 62 , 63 ], endogenous retroviruses [ 64 , 65 , 66 , 67 ], and the neutrophil–lymphocyte ratio [ 68 , 69 ]. Although there are no definitive biomarkers of clinical impact, many studies are currently ongoing.…”

Immune Checkpoint Inhibitor in First-Line Treatment of Metastatic Renal Cell Carcinoma: A Review of Current Evidence and Future Directions

“…Neutrophil lymphocyte ratio (NLR) is a measure of inflammation secondary to tumour growth and is the ratio of absolute neutrophil count to absolute lymphocyte count, which has been postulated as a potential biomarker that predicts treatment response to immune checkpoint inhibitor (41,42). NLR may also be a negative prognostic factor as high NLR is associated with higher risk of death and treatment failure (41,42).…”

“…Neutrophil lymphocyte ratio (NLR) is a measure of inflammation secondary to tumour growth and is the ratio of absolute neutrophil count to absolute lymphocyte count, which has been postulated as a potential biomarker that predicts treatment response to immune checkpoint inhibitor (41,42). NLR may also be a negative prognostic factor as high NLR is associated with higher risk of death and treatment failure (41,42). There are small studies to suggest that reduction of NLR pre-treatment and after treatment is associated with improved outcomes in those treated with immune checkpoint inhibitor in advanced RCC (41,42).…”

“…NLR may also be a negative prognostic factor as high NLR is associated with higher risk of death and treatment failure (41,42). There are small studies to suggest that reduction of NLR pre-treatment and after treatment is associated with improved outcomes in those treated with immune checkpoint inhibitor in advanced RCC (41,42). However, the value of NLR as a biomarker requires further investigation.…”