Impact of Lymphopenia on Treatment Outcomes in Unresectable Non-Small Cell Lung Cancer

Abstract

The purpose of this study was to investigate associations between lymphopenia and radiotherapy (RT) parameters. Moreover, to investigate the prognostic role of lymphopenia, and treatment and patient-related factors. Definitive chemoradiation (CRT) with consolidative durvalumab offers the best chance for cure in patients with unresectable, locally advanced non-small cell lung cancer. However, treatment-related lymphopenia (TRL) may negatively impact outcomes. Fifty-four patients treated with CRT and durvalumab from 2017 to 2021 at a single academic center were prospectively included. Absolute lymphocyte counts (ALC), absolute neutrophil counts (ANC), and neutrophil-to lymphocyte ratio (NLR) were analyzed before (TLR1), and after CRT (TRL2), before durvalumab initiation (TRL3), and 3 months after CRT (TRL4). Patients were prospectively enrolled in the study. Categorical variables were analyzed using Pearson's chi-squared or Fisher's Exact tests. Nonparametric continuous variables were analyzed using Wilcoxon Rank-Sum test. Association of continuous clinical and dosimetric variables with hematologic toxicity was performed with Spearman's correlation. Kaplan-Meier analysis and the log-rank test were used to assess the probability of PFS and OS Cox proportional hazard models were used to estimate the effect of covariates on disease control rate. Variables that were strongly associated in univariate Cox regression analyses were entered into a multivariable Cox model. All statistical tests were two-sided, and statistical significance was set at p < 0.05. All analyses were performed using STATA version 15.1. The median follow-up was 28.4 months (m). N2-3 disease showed worse TRL2 compared to N0-1 (p = 0.013). Table 1 shows RT parameters related to TLR2. Median time to durvalumab initiation after CRT was 47 days. Patients who started durvalumab later than 42 days had a greater decrease in lymphocytes at the end of CRT compared to those who started earlier. (70.1 vs 58.8%, p = 0.025). Median overall survival (OS) and progression-free survival (PFS) were 39.4 and 22.4m, respectively. Disease control rate (DCR) with durvalumab consolidation was 70.8%. Patients with NLR >4 prior to durvalumab initiation achieved a lower DCR compared to those with a NLR ≤4 (85.7 vs 14.3%, p = 0.005). CRT-related immunosuppression is associated with delayed durvalumab initiation and worse DCR. Larger PTV and higher lung and heart doses are associated with TRL. Median real-world OS and PFS are similar to those in the PACIFIC trial.