Association of severe lymphopenia and disease progression in unresectable locally advanced non-small cell lung cancer treated with definitive chemoradiation and immunotherapy

被引：44

作者：

Friedes, Cole ^{[1
]}

Chakrabarti, Turja ^{[2
]}

Olson, Sarah ^{[3
]}

Prichett, Laura ^{[3
]}

Brahmer, Julie R. ^{[4
]}

Forde, Patrick M. ^{[4
]}

Voong, Ranh K. ^{[1
]}

Marrone, Kristen A. ^{[4
]}

Lam, Vincent K. ^{[4
]}

Hann, Christine L. ^{[4
]}

Broderick, Stephen R. ^{[5
]}

Battafarano, Richard J. ^{[5
]}

Ha, Jinny S. ^{[5
]}

Bush, Errol L. ^{[5
]}

Yang, Stephen C. ^{[5
]}

Hales, Russel K. ^{[1
]}

Feliciano, Josephine L. ^{[4
]}

机构：

[1] Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Sch Med, Baltimore, MD 21224 USA

[2] Johns Hopkins Bayview Med Ctr, Dept Med, Baltimore, MD 21224 USA

[3] Johns Hopkins Bayview Med Ctr, Biostat Epidemiol & Data Management Core BEAD, Baltimore, MD 21224 USA

[4] Johns Hopkins Univ, Dept Oncol, Sch Med, Baltimore, MD 21224 USA

[5] Johns Hopkins Univ, Dept Thorac Surg, Sch Med, Baltimore, MD 21224 USA

来源：

LUNG CANCER | 2021年 / 154卷

关键词：

PACIFIC; Immunotherapy; ICI; Lymphopenia; NSCLC; Treatment-related lymphopenia; TO-LYMPHOCYTE RATIO; RADIATION-THERAPY; STAGE IIIA; RADIOTHERAPY; SURVIVAL; SUBPOPULATIONS; CHEMOTHERAPY; INHIBITORS;

D O I：

10.1016/j.lungcan.2021.01.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Definitive chemoradiation with consolidative immunotherapy offers the best chance for cure in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC). However, treatment-related lymphopenia (TRL) may negatively impact outcomes. Methods: Patients definitively treated with chemoradiation and immunotherapy from 2015 to 2019 at a single tertiary academic center were identified. Severe lymphopenia was defined as <0.5 ? 109 cells/L. Progressionfree survival (PFS) was calculated by Kaplan Meier methodology. Univariate and multivariate Cox Proportional Hazard modeling was used to correlate clinical variables with disease outcome. Immune-related adverse events (irAEs) were assessed according to CTCAE version 5.0 criteria. Results: Seventy-eight patients were included in the final cohort. The median age was 66 years (IQR: 58-73), 55 % were males, and 88 % had a KPS of >70. At baseline, 90 % (n = 70/78) of patients had a normal ALC and one patient had severe lymphopenia. After chemoradiation, the median ALC decreased from 1.52 ? 109cells/L (IQR: 1.23?1.98) to 0.72 ? 109cells/L (IQR: 0.52-0.94) (p < 0.001), 22 % (n = 17/78) of patients had a normal ALC, and 23 % (n = 18/78) of patients developed severe lymphopenia. Patients who initiated consolidative immunotherapy with severe lymphopenia had worse PFS than those who did not (median 217 days [IQR: 120?434] vs. 570 days [IQR: 401-NR], p < 0.001). On multivariate modeling, severe lymphopenia at the time of immunotherapy initiation remained an independent predictor of worse PFS (HR 4.90, p < 0.001). Conclusions: This is the first report to associate severe TRL with disease progression in patients with locally advanced NSCLC receiving consolidative immunotherapy. Factors associated with development of lymphopenia and strategies to mitigate lymphopenic effects should be considered.

引用

页码：36 / 43

页数：8

共 42 条

[1] Radiotherapy-Related Lymphopenia Affects Overall Survival in Patients With Lung Cancer [J].

Abravan, Azadeh ;

Faivre-Finn, Corinne ;

Kennedy, Jason ;

McWilliam, Alan ;

van Herk, Marcel .

JOURNAL OF THORACIC ONCOLOGY, 2020, 15 (10) :1624-1635

[2] Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial [J].

Albain, Kathy S. ;

Swann, R. Suzanne ;

Rusch, Valerie W. ;

Turrisi, Andrew T., III ;

Shepherd, Frances A. ;

Smith, Colum ;

Chen, Yuhchyau ;

Livingston, Robert B. ;

Feins, Richard H. ;

Gandara, David R. ;

Fry, Willard A. ;

Darling, Gail ;

Johnson, David H. ;

Green, Mark R. ;

Miller, Robert C. ;

Ley, Joanne ;

Sause, Willliam T. ;

Cox, James D. .

LANCET, 2009, 374 (9687) :379-386

[3] Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC [J].

Antonia, S. J. ;

Villegas, A. ;

Daniel, D. ;

Vicente, D. ;

Murakami, S. ;

Hui, R. ;

Kurata, T. ;

Chiappori, A. ;

Lee, K. H. ;

de Wit, M. ;

Cho, B. C. ;

Bourhaba, M. ;

Quantin, X. ;

Tokito, T. ;

Mekhail, T. ;

Planchard, D. ;

Kim, Y. -C. ;

Karapetis, C. S. ;

Hiret, S. ;

Ostoros, G. ;

Kubota, K. ;

Gray, J. E. ;

Paz-Ares, L. ;

Carpeno, J. de Castro ;

Faivre-Finn, C. ;

Reck, M. ;

Vansteenkiste, J. ;

Spigel, D. R. ;

Wadsworth, C. ;

Melillo, G. ;

Taboada, M. ;

Dennis, P. A. ;

Ozguroglu, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (24) :2342-2350

[4] Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer [J].

Antonia, S. J. ;

Villegas, A. ;

Daniel, D. ;

Vicente, D. ;

Murakami, S. ;

Hui, R. ;

Yokoi, T. ;

Chiappori, A. ;

Lee, K. H. ;

de Wit, M. ;

Cho, B. C. ;

Bourhaba, M. ;

Quantin, X. ;

Tokito, T. ;

Mekhail, T. ;

Planchard, D. ;

Kim, Y. -C. ;

Karapetis, C. S. ;

Hiret, S. ;

Ostoros, G. ;

Kubota, K. ;

Gray, J. E. ;

Paz-Ares, L. ;

de Castro Carpeno, J. ;

Wadsworth, C. ;

Melillo, G. ;

Jiang, H. ;

Huang, Y. ;

Dennis, P. A. ;

Ozguroglu, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (20) :1919-1929

[5] Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis [J].

Benedict Sacdalan, Danielle ;

Anne Lucero, Josephine ;

Lee Sacdalan, Dennis .

ONCOTARGETS AND THERAPY, 2018, 11 :955-965

[6] Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study [J].

Bradley, Jeffrey D. ;

Paulus, Rebecca ;

Komaki, Ritsuko ;

Masters, Gregory ;

Blumenschein, George ;

Schild, Steven ;

Bogart, Jeffrey ;

Hu, Chen ;

Forster, Kenneth ;

Magliocco, Anthony ;

Kavadi, Vivek ;

Garces, Yolanda I. ;

Narayan, Samir ;

Iyengar, Puneeth ;

Robinson, Cliff ;

Wynn, Raymond B. ;

Koprowski, Christopher ;

Meng, Joanne ;

Beitler, Jonathan ;

Gaur, Rakesh ;

Curran, Walter, Jr. ;

Choy, Hak .

LANCET ONCOLOGY, 2015, 16 (02) :187-199

[7] The Role of Tumor-Infiltrating Immune Cells and Chronic Inflammation at the Tumor Site on Cancer Development, Progression, and Prognosis Emphasis on Non-small Cell Lung Cancer [J].

Bremnes, Roy M. ;

Al-Shibli, Khalid ;

Donnem, Tom ;

Sirera, Rafael ;

Al-Saad, Samer ;

Andersen, Sigve ;

Stenvold, Helge ;

Camps, Carlos ;

Busund, Lill-Tove .

JOURNAL OF THORACIC ONCOLOGY, 2011, 6 (04) :824-833

[8]

CAMPBELL AC, 1976, CLIN EXP IMMUNOL, V23, P200

[9] Association between severe treatment-related lymphopenia and progression-free survival in patients with newly diagnosed squamous cell head and neck cancer [J].

Campian, Jian L. ;

Sarai, Guneet ;

Ye, Xiaobu ;

Marur, Shanthi ;

Grossman, Stuart A. .

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2014, 36 (12) :1747-1753

[10] Treatment-related Lymphopenia in Patients With Stage III Non-Small-Cell Lung Cancer [J].

Campian, Jian L. ;

Ye, Xiaobu ;

Brock, Malcolm ;

Grossman, Stuart A. .

CANCER INVESTIGATION, 2013, 31 (03) :183-188

← 1 2 3 4 5 →