Impact of Treatment-Related Lymphopenia on Immunotherapy for Advanced Non-Small Cell Lung Cancer

Purpose: The interest in combining radiation therapy (RT) with immunotherapy is increasing. We investigated the significance of lymphopenia in patients receiving immunotherapy for non-small cell lung cancer (NSCLC), and the factors associated with treatment-related lymphopenia, with particular emphasis on RT. Methods and Methods: In this retrospective single institution study, 268 patients with advanced NSCLC received immunotherapy, of whom 146 received RT. Lymphopenia was defined as an absolute lymphocyte count <1000 cells/mm.³ Patients were divided into 2 groups depending on the presence of peri-immunotherapy lymphopenia at the start of immunotherapy or during immunotherapy. Results: At median 6.4 months of follow-up, patients with peri-immunotherapy lymphopenia (n = 146; 54.5%) showed significantly poorer progression-free survival (PFS) (median PFS: 2.2 vs 5.9 months, P <.001) and overall survival (OS) (median OS: 5.7 vs 12.1 months, P <.001). On multivariate analysis, peri-immunotherapy lymphopenia remained a significant prognostic factor for both PFS and OS. RT significantly increased peri-immunotherapy lymphopenia with an odds ratio (OR) of 1.91 (P =.025). Factors associated with the development of RT-associated lymphopenia included multiple courses (OR, 3.78; P <.001), multiple irradiated sites (OR, 4.77; P =.018), and higher dose (≥50 Gy) (OR, 3.75; P =.004). Conversely, stereotactic body RT/radiosurgery reduced the risk (OR 0.21; P =.002). Conclusions: Lymphopenia was indicative of poor prognosis in NSCLC patients receiving immunotherapy and was significantly associated with more intensive RT. Choosing appropriate RT regimens and techniques may be essential in reducing lymphopenia. Promising results are expected in the era of precision RT.