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

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

JTO Clinical and Research Reports (Sep 2022)

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

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

Affiliations

Wang Jing, MD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Oncology, Jinan Central Hospital, Shandong First Medical University, Shandong, People’s Republic of China
Ting Xu, PhD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Lirong Wu, MD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; 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
Pablo B. Lopez, MD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Clemens Grassberger, PhD: Radiation-Drug Treatment Design Lab, Massachusetts General Hospital, Boston, Massachusetts
Susannah G. Ellsworth, MD: Gastrointestinal Malignancies Service, Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Radhe Mohan, PhD: Department of Population Health, The University of Texas at Austin, Austin, Texas
Brian P. Hobbs, PhD: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas
George R. Blumenschein, MD: Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Janet Tu, MD: Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Mehmet Altan, MD: Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Percy Lee, MD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Zhongxing Liao, MD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Steven H. Lin, MD, PhD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Corresponding author. Address correspondence to: Steven H. Lin, MD, PhD, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.

Journal volume & issue: Vol. 3, no. 9
p. 100391

Abstract

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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.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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