The impact of pretreatment absolute lymphocyte count (pALC) and neutrophil-lymphocyte ratio (pNLR) on checkpoint inhibitors (CPIs) response rates in renal cell carcinoma (RCC) and bladder urothelial cancers (BC).

Abstract

31 Background: CPIs have been established as essential components of cancer immunotherapy across multiple cancer types with proven clinical benefit, improved outcomes, and less toxicity. Studies in lung and head and neck cancers found that low ALC, a marker of immune exhaustion, was associated with poor response to CPIs and worse progression-free survival. We explored the effect of pALC and pNLR on CPI response rates in patients with RCC and BC. Methods: We retrospectively reviewed every RCC and BC patient that received CPIs at Overton Brooks VA Medical Center and LSUHSC-S between 2015 and 2019. Patients’ pALC and pNLR were calculated. The patients were divided according to pALC into 2 groups: Group A with pALC > 1000 and Group B with pALC < 1000. Similarly, using NLR’s established upper normal limit of 3, 2 groups were created: Group 1 with pNLR < 3 and Group 2 with pNLR > 3. Our primary outcome of interest was defined as the presence or absence of CPI response. Patients who attained stable disease, partial response, and complete response were categorized as responders. Those who progressed on CPIs were labeled as non-responders. The significance of the association between pALC and pNLR groups and the occurrence of any response was analyzed statistically. Results: Twenty patients (13 RCC, 7 BC) were treated with CPIs and had documented responses. Twelve patients had pALC > 1000 (Group A) whereas 8 patients had pALC < 1000 (Group B). Both groups were comparable with respect to age, sex, race, and types of CPIs. Group A had a significantly higher response rate (75% vs 25%, p = 0.027). As to pNLR, 10 patients had pNLR < 3 (Group 1) and another 10 patients had pNLR > 3 (Group 2). Patients with pNLR > 3 had worse response rates to CPIs compared to those with pNLR < 3 (30% vs 80%, p = 0.024). Conclusions: This is the first report from a real-world clinical setting to show a detrimental association between pALC < 1000 and pNLR > 3 and CPI response rates in a retrospective cohort of consecutive non-selected kidney and bladder cancer patients. This association and its clinical utility require further confirmation in a prospective larger cohort.