Friedes C, Chakrabarti T, Olson S, et al. - For patients suffering from unresectable, locally advanced non-small cell lung cancer (NSCLC), definitive chemoradiation with consolidative immunotherapy provides the greatest chance for cure, but outcomes may be negatively impacted by treatment-related lymphopenia (TRL), so researchers evaluated the impact of TRL on outcomes. They analyzed 78 patients with a median age of 66 years who were definitively managed with chemoradiation and immunotherapy from 2015-2019. A normal ALC was present in 90% (n = 70/78) of patients at baseline; severe lymphopenia was detected in one patient. Following chemoradiation, a reduction in median ALC from 1.52 × 10 ⁹cells/L to 0.72 × 10 ⁹cells/L was detected. A normal ALC was identified in 22% (n = 17/78) of patients, and severe lymphopenia occurred in 23% (n = 18/78) of patients. Worse progression-free survival was independently predicted by severe lymphopenia at the time of immunotherapy initiation, as seen in multivariate modeling. In patients suffering from locally advanced NSCLC undergoing consolidative immunotherapy, this study represents the first to associate severe TRL with disease progression. Consideration should be given to factors related to lymphopenia development as well as strategies to mitigate lymphopenic impacts.