Cargando…

Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis

BACKGROUND: Myocarditis attributable to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune‐related adverse event. Limited data have suggested an association between baseline and on‐treatment absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) and the developmen...

Descripción completa

Detalles Bibliográficos
Autores principales: Drobni, Zsofia D., Zafar, Amna, Zubiri, Leyre, Zlotoff, Daniel A., Alvi, Raza M., Lee, Charlotte, Hartmann, Sarah, Gilman, Hannah K., Villani, Alexandra‐Chloe, Nohria, Anju, Groarke, John D., Sullivan, Ryan J., Reynolds, Kerry L., Zhang, Lili, Neilan, Tomas G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763791/
https://www.ncbi.nlm.nih.gov/pubmed/33190570
http://dx.doi.org/10.1161/JAHA.120.018306
_version_ 1783628102282248192
author Drobni, Zsofia D.
Zafar, Amna
Zubiri, Leyre
Zlotoff, Daniel A.
Alvi, Raza M.
Lee, Charlotte
Hartmann, Sarah
Gilman, Hannah K.
Villani, Alexandra‐Chloe
Nohria, Anju
Groarke, John D.
Sullivan, Ryan J.
Reynolds, Kerry L.
Zhang, Lili
Neilan, Tomas G.
author_facet Drobni, Zsofia D.
Zafar, Amna
Zubiri, Leyre
Zlotoff, Daniel A.
Alvi, Raza M.
Lee, Charlotte
Hartmann, Sarah
Gilman, Hannah K.
Villani, Alexandra‐Chloe
Nohria, Anju
Groarke, John D.
Sullivan, Ryan J.
Reynolds, Kerry L.
Zhang, Lili
Neilan, Tomas G.
author_sort Drobni, Zsofia D.
collection PubMed
description BACKGROUND: Myocarditis attributable to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune‐related adverse event. Limited data have suggested an association between baseline and on‐treatment absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) and the development of other immune‐related adverse events; there are no data characterizing the role of ALC and NLR in ICI‐associated myocarditis. METHODS AND RESULTS: This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post‐ICI immune‐related adverse events. We leveraged clinical testing, where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events was also tested. In cases, there was a statistically significant decrease in ALC with myocarditis from baseline (1.6 thousands per cubic milliliter (K/μL); interquartile range, 1.1–1.9 K/μL) to admission (1.1 K/μL; interquartile range, 0.7–1.3 K/μL; P<0.001). Similarly, there was an increase in NLR from baseline (3.5; interquartile range, 2.3–5.4) to admission (6.6; interquartile range, 4.5–14.1; P<0.001). There was no statistically significant change in controls. In follow‐up, there were 20 events; larger decreases in ALC (44.6% versus 18.2%; P<0.001) or increases in NLR (156.5% versus 65.1%; P=0.019) were associated with major adverse cardiac events. CONCLUSIONS: A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR was associated with subsequent major adverse cardiac events.
format Online
Article
Text
id pubmed-7763791
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-77637912020-12-28 Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis Drobni, Zsofia D. Zafar, Amna Zubiri, Leyre Zlotoff, Daniel A. Alvi, Raza M. Lee, Charlotte Hartmann, Sarah Gilman, Hannah K. Villani, Alexandra‐Chloe Nohria, Anju Groarke, John D. Sullivan, Ryan J. Reynolds, Kerry L. Zhang, Lili Neilan, Tomas G. J Am Heart Assoc Original Research BACKGROUND: Myocarditis attributable to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune‐related adverse event. Limited data have suggested an association between baseline and on‐treatment absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) and the development of other immune‐related adverse events; there are no data characterizing the role of ALC and NLR in ICI‐associated myocarditis. METHODS AND RESULTS: This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post‐ICI immune‐related adverse events. We leveraged clinical testing, where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events was also tested. In cases, there was a statistically significant decrease in ALC with myocarditis from baseline (1.6 thousands per cubic milliliter (K/μL); interquartile range, 1.1–1.9 K/μL) to admission (1.1 K/μL; interquartile range, 0.7–1.3 K/μL; P<0.001). Similarly, there was an increase in NLR from baseline (3.5; interquartile range, 2.3–5.4) to admission (6.6; interquartile range, 4.5–14.1; P<0.001). There was no statistically significant change in controls. In follow‐up, there were 20 events; larger decreases in ALC (44.6% versus 18.2%; P<0.001) or increases in NLR (156.5% versus 65.1%; P=0.019) were associated with major adverse cardiac events. CONCLUSIONS: A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR was associated with subsequent major adverse cardiac events. John Wiley and Sons Inc. 2020-11-16 /pmc/articles/PMC7763791/ /pubmed/33190570 http://dx.doi.org/10.1161/JAHA.120.018306 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Drobni, Zsofia D.
Zafar, Amna
Zubiri, Leyre
Zlotoff, Daniel A.
Alvi, Raza M.
Lee, Charlotte
Hartmann, Sarah
Gilman, Hannah K.
Villani, Alexandra‐Chloe
Nohria, Anju
Groarke, John D.
Sullivan, Ryan J.
Reynolds, Kerry L.
Zhang, Lili
Neilan, Tomas G.
Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis
title Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis
title_full Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis
title_fullStr Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis
title_full_unstemmed Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis
title_short Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor–Associated Myocarditis
title_sort decreased absolute lymphocyte count and increased neutrophil/lymphocyte ratio with immune checkpoint inhibitor–associated myocarditis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763791/
https://www.ncbi.nlm.nih.gov/pubmed/33190570
http://dx.doi.org/10.1161/JAHA.120.018306
work_keys_str_mv AT drobnizsofiad decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT zafaramna decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT zubirileyre decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT zlotoffdaniela decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT alvirazam decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT leecharlotte decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT hartmannsarah decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT gilmanhannahk decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT villanialexandrachloe decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT nohriaanju decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT groarkejohnd decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT sullivanryanj decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT reynoldskerryl decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT zhanglili decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis
AT neilantomasg decreasedabsolutelymphocytecountandincreasedneutrophillymphocyteratiowithimmunecheckpointinhibitorassociatedmyocarditis