Early peripheral blood neutrophil/lymphocyte ratio (NLR) dynamics to predict primary refractory disease in metastatic urothelial carcinoma (mUC) patients receiving PD1/L1 inhibitors.

Abstract

793 Background: Early identification of refractory vs. sensitive disease may inform precision medicine in patients (pts) with advanced malignancies receiving systemic therapy. While circulating tumor (ct)-DNA may be employed to detect early tumor burden dynamics, the access to the assay presents challenges in globalization. We have previously reported that an increase in peripheral blood NLR in the first 3-4 weeks after initiating PD1/L1 inhibitors for 144 patients with mUC was inversely associated with any regression of tumor (ART) (Thomas J, Genitourinary Cancer Symposium Feb 2022). We aimed to further investigate the impact of early dynamics in NLR as well as other readily available clinical and laboratory factors for the early discrimination of benefit from PD1/L1 inhibitors in pts with mUC. Methods: Deidentified data from mUC pts who were treated with PD1/L1 inhibitors at AdventHealth institutions in the US were reviewed retrospectively. Demographic data (age, sex), setting (untreated vs. post-therapy), sites of metastasis and performance status (PS) were collected. Additionally, clinical and laboratory variables were collected at baseline and 3-4 weeks after initiating the PD1/L1 inhibitor including body weight, NLR, platelets, eosinophils, albumin and hemoglobin. We assessed the association of dynamics in these factors with the best response category of progressive disease (PD) per RECIST1.1 and any regression of tumor (ART). Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 76 pts were evaluable. The median age was 69.5 years, 54 (71.05%) were male, and 24 (31.58%) were therapy naive. ART and PD as best response were seen in 38 (50%) and 34 (44.74%) pts, respectively. Multivariable logistic regression identified an increase in NLR to be associated with refractory disease and poor regression rate, i.e. PD as best response and absence of ART. The OR was 12.21 (95% CI 1.21–123.71, p = 0.034) for PD vs. the others (AUC 0.72), and 5.6 (95% CI 1.48– 21.13, p = 0.02) for absence of ART vs ART (AUC 0.7). Dynamics of other factors did not reach statistical significance. Conclusions: Our retrospective analysis demonstrates that early NLR dynamics, specifically an increase in 3-4 weeks, was validated to be associated with absence of tumor regression and was robustly associated with primary refractory disease in patients with mUC receiving PD1/L1 inhibitor therapy. Given the affordability and global availability of peripheral blood NLR, validation in large datasets is warranted in conjunction with its performance vs. ctDNA. Early identification of primary refractory disease may allow modification or intensification of therapy before clinical decline to improve long-term clinical outcomes.