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

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

doi:10.1016/j.jtocrr.2022.100391

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

JTO Clin Res Rep. 2022 Aug 7;3(9):100391. doi: 10.1016/j.jtocrr.2022.100391. eCollection 2022 Sep.

Authors

Wang Jing^{1

2}, Ting Xu¹, Lirong Wu^{1

3}, Pablo B Lopez¹, Clemens Grassberger⁴, Susannah G Ellsworth⁵, Radhe Mohan⁶, Brian P Hobbs⁷, George R Blumenschein⁸, Janet Tu⁸, Mehmet Altan⁸, Percy Lee¹, Zhongxing Liao¹, Steven H Lin¹

Affiliations

¹ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
² Department of Oncology, Jinan Central Hospital, Shandong First Medical University, Shandong, People's Republic of China.
³ Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
⁴ Radiation-Drug Treatment Design Lab, Massachusetts General Hospital, Boston, Massachusetts.
⁵ Gastrointestinal Malignancies Service, Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁶ Department of Population Health, The University of Texas at Austin, Austin, Texas.
⁷ Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
⁸ Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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: Consolidative therapy; Durvalumab; Immunotherapy; Lymphopenia; NSCLC; Radiation.