Severe Radiation-Induced Lymphopenia Attenuates the Benefit of Durvalumab After Concurrent Chemoradiotherapy for NSCLC

Authors

Wang Jing
Ting Xu
Lirong Wu
Pablo B Lopez
Clemens Grassberger
Susannah G Ellsworth
Radhe Mohan
Brian P Hobbs
George R Blumenschein
Janet Tu
Mehmet Altan
Percy Lee
Zhongxing Liao
Steven H Lin

Publication Date

9-1-2022

Journal

JTO Clinical and Research Reports

DOI

10.1016/j.jtocrr.2022.100391

PMID

36089921

PMCID

PMC9449658

PubMedCentral® Posted Date

8-7-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Durvalumab after concurrent chemoradiation (CCRT) for NSCLC improves survival, but only in a subset of patients. We investigated the effect of severe radiation-induced lymphopenia (sRIL) on survival in these patients.

Methods: Outcomes after CCRT (2010-2019) or CCRT followed by durvalumab (2018-2019) were reviewed. RIL was defined by absolute lymphocyte count (ALC) nadir in samples collected at end of CCRT; sRIL was defined as nadir ALC less than 0.23 × 109/L (the lowest tertile). Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Cox proportional hazard modeling evaluated associations between clinical variables and survival.

Results: Of 309 patients, 192 (62%) received CCRT only and 117 (38%) CCRT plus durvalumab. Multivariable logistic regression analysis indicated that sRIL was associated with planning target volume (OR = 1.002, p = 0.001), stage IIIB disease (OR = 2.77, p = 0.04), and baseline ALC (OR = 0.36, p < 0.01). Durvalumab extended median PFS (23.3 versus 14.1 mo, p = 0.003) and OS (not reached versus 30.8 mo, p < 0.01). sRIL predicted poorer PFS and OS in both treatment groups. Among patients with sRIL, durvalumab did not improve survival (median = 24.6 mo versus 18.1 mo CCRT only, p = 0.079). On multivariable analyses, sRIL (OR = 1.81, p < 0.01) independently predicted poor survival.

Conclusions: Severe RIL compromises survival benefits from durvalumab after CCRT for NSCLC. Measures to mitigate RIL after CCRT may be warranted to enhance the benefit of consolidation durvalumab.

Keywords

NSCLC, Lymphopenia, Radiation, Immunotherapy, Durvalumab, Consolidative therapy

Published Open-Access

yes

Recommended Citation

Jing, Wang; Xu, Ting; Wu, Lirong; et al., "Severe Radiation-Induced Lymphopenia Attenuates the Benefit of Durvalumab After Concurrent Chemoradiotherapy for NSCLC" (2022). Faculty, Staff and Student Publications. 4749.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4749