Abstract 2021: Impact of corticosteroids on predictive and prognostic value of neutrophil-to-lymphocyte ratio in patients with non-small cell lung cancer treated with immune checkpoint inhibitor therapy

Abstract Introduction: An elevated baseline neutrophil-to-lymphocyte ratio (NLR) can signal an imbalance between pro-tumor and anti-tumor inflammatory responses and has been associated with worse overall survival (OS) and lower response rates in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Corticosteroids, known to cause neutrophilia and lymphopenia, are widely used in NSCLC, but their impact on biomarker performance remains elusive. This study investigates how baseline steroid use affects biomarker performance in NSCLC patients on ICIs. Methods: We retrospectively evaluated 252 patients with NSCLC treated with ICIs at the Roswell Park Comprehensive Cancer Center (RPCCC) (n=81) (discovery cohort) and the University of Southern California (USC) (n=171) (validation cohort). We analyzed the association between baseline NLR at ICI initiation with overall response rate (ORR), progression free survival (PFS), and OS. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. Patients were stratified by NLR: NLR ≥ 5 (high) and NLR < 5 (low). ORR was estimated using Fisher’s exact test, and Kaplan-Meier survival distributions for PFS and OS were generated. Results: In our cohort, 159 (63.1%) of 252 patients had an NLR < 5 and 93 (33.9%) had NLR ≥ 5. NLR < 5 at baseline was correlated with longer PFS (RPCCC: p<0.0005; USC: p<0.005) and OS (RPCCC: p<0.0005; USC: p<0.05) although there was no significant relationship between NLR and treatment response rates in RPCCC or USC cohorts. We identified 19 patients who were on systemic steroids at the time of initiation of ICI therapy. Indications for corticosteroids were brain metastases or comorbid lung conditions such as COPD, and all 19 patients remained on steroids for at least 12 weeks from the initiation of ICI therapy. When examining the predictive value of NLR by steroid and non-steroid subgroups in both cohorts, we found no significant association between NLR and treatment response rates for patients taking steroids and patients not taking steroids. Patients not taking steroids with low NLR showed markedly longer PFS (RPCCC: p<0.005; USC: p<0.05) and OS (RPCCC: p<0.001; USC: p<0.05). However, patients taking steroids showed no significant correlation of NLR with PFS or OS. Conclusions: Baseline NLR was associated with prognosis of NSCLC patients undergoing ICI therapy who do not receive steroids at the initiation of ICI therapy but was not correlated with response to ICI therapy. The results of NLR can be obtained via routine bloodwork and readily available for prompt feedback to oncologists and patients; however, clinicians must take care in the prognostic value of NLR in patients who were on steroids at the initiation of ICI therapy. Citation Format: Angelina Lim, Alexandra Meyer, Lauren Polyakov, Ryan Cooper, Aubree Mades, Shirley Ye, Joshua Ni, Hongbin Chen, Leslie Contreras, Joy Sarkar, Rajeev Sharma, Brahm H. Segal, Robert Hsu, Jorge Nieva, Grace K. Dy, Fumito Ito. Impact of corticosteroids on predictive and prognostic value of neutrophil-to-lymphocyte ratio in patients with non-small cell lung cancer treated with immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2021.