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

Cole Friedes; Turja Chakrabarti; Sarah Olson; Laura Prichett; Julie R. Brahmer; Patrick J. Forde; Ranh K. Voong; Kristen A. Marrone; Vincent K. Lam; Christine L. Hann; Stephen R. Broderick; Richard J. Battafarano; Jinny S. Ha; Errol L. Bush; Stephen C. Yang; Russel K. Hales; Josephine L. Feliciano

doi:10.1016/j.lungcan.2021.01.022

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

Cole Friedes, Turja Chakrabarti, Sarah Olson, Laura Prichett, Julie R. Brahmer, Patrick J. Forde, Ranh K. Voong, Kristen A. Marrone, Vincent K. Lam, Christine L. Hann, Stephen R. Broderick, Richard J. Battafarano, Jinny S. Ha, Errol L. Bush, Stephen C. Yang, Russel K. Hales, Josephine L. Feliciano

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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. Progression-free 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.

Original language	English (US)
Pages (from-to)	36-43
Number of pages	8
Journal	Lung Cancer
Volume	154
DOIs	https://doi.org/10.1016/j.lungcan.2021.01.022
State	Published - Apr 2021

Keywords

ICI
Immunotherapy
Lymphopenia
NSCLC
PACIFIC
Treatment-related lymphopenia

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

Access to Document

10.1016/j.lungcan.2021.01.022

Cite this

Friedes, C., Chakrabarti, T., Olson, S., Prichett, L., Brahmer, J. R., Forde, P. J., Voong, R. K., Marrone, K. A., Lam, V. K., Hann, C. L., Broderick, S. R., Battafarano, R. J., Ha, J. S., Bush, E. L., Yang, S. C., Hales, R. K., & Feliciano, J. L. (2021). Association of severe lymphopenia and disease progression in unresectable locally advanced non-small cell lung cancer treated with definitive chemoradiation and immunotherapy. Lung Cancer, 154, 36-43. https://doi.org/10.1016/j.lungcan.2021.01.022

Friedes, C, Chakrabarti, T, Olson, S, Prichett, L , Brahmer, JR , Forde, PJ , Voong, RK , Marrone, KA , Lam, VK , Hann, CL , Broderick, SR , Battafarano, RJ , Ha, JS , Bush, EL , Yang, SC , Hales, RK & Feliciano, JL 2021, 'Association of severe lymphopenia and disease progression in unresectable locally advanced non-small cell lung cancer treated with definitive chemoradiation and immunotherapy', Lung Cancer, vol. 154, pp. 36-43. https://doi.org/10.1016/j.lungcan.2021.01.022

@article{8706142abe774172aa36c1f93cfc599d,

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

abstract = "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. Progression-free 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.",

keywords = "ICI, Immunotherapy, Lymphopenia, NSCLC, PACIFIC, Treatment-related lymphopenia",

author = "Cole Friedes and Turja Chakrabarti and Sarah Olson and Laura Prichett and Brahmer, {Julie R.} and Forde, {Patrick J.} and Voong, {Ranh K.} and Marrone, {Kristen A.} and Lam, {Vincent K.} and Hann, {Christine L.} and Broderick, {Stephen R.} and Battafarano, {Richard J.} and Ha, {Jinny S.} and Bush, {Errol L.} and Yang, {Stephen C.} and Hales, {Russel K.} and Feliciano, {Josephine L.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = apr,

doi = "10.1016/j.lungcan.2021.01.022",

language = "English (US)",

volume = "154",

pages = "36--43",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Association of severe lymphopenia and disease progression in unresectable locally advanced non-small cell lung cancer treated with definitive chemoradiation and immunotherapy

AU - Friedes, Cole

AU - Chakrabarti, Turja

AU - Olson, Sarah

AU - Prichett, Laura

AU - Brahmer, Julie R.

AU - Forde, Patrick J.

AU - Voong, Ranh K.

AU - Marrone, Kristen A.

AU - Lam, Vincent K.

AU - Hann, Christine L.

AU - Broderick, Stephen R.

AU - Battafarano, Richard J.

AU - Ha, Jinny S.

AU - Bush, Errol L.

AU - Yang, Stephen C.

AU - Hales, Russel K.

AU - Feliciano, Josephine L.

PY - 2021/4

Y1 - 2021/4

N2 - 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. Progression-free 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.

AB - 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. Progression-free 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.

KW - ICI

KW - Immunotherapy

KW - Lymphopenia

KW - NSCLC

KW - PACIFIC

KW - Treatment-related lymphopenia

UR - http://www.scopus.com/inward/record.url?scp=85100884421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85100884421&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2021.01.022

DO - 10.1016/j.lungcan.2021.01.022

M3 - Article

C2 - 33611224

AN - SCOPUS:85100884421

SN - 0169-5002

VL - 154

SP - 36

EP - 43

JO - Lung Cancer

JF - Lung Cancer

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this