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

Yeona Cho, Sangjoon Park, Hwa Kyung Byun, Chang Geol Lee, Jaeho Cho, Min Hee Hong, Hye Ryun Kim, Byoung Chul Cho, Sinae Kim, Juyoung Park, Hong In Yoon

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1065-1073
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number5
Publication statusPublished - 2019 Dec 1

Bibliographical note

Funding Information:
This work was supported by Ministry of Science, Korea through the R&D program of NRF-2017M3A9E8029717.

Publisher Copyright:
© 2019 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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