Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.
immune checkpoint inhibitors
non-small cell lung cancer
steroids
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
2019
2019
Historique:
received:
11
10
2018
revised:
09
11
2018
accepted:
26
12
2018
entrez:
10
4
2019
pubmed:
10
4
2019
medline:
10
4
2019
Statut:
epublish
Résumé
Steroids are frequently used in patients with metastatic non-small cell lung cancer (mNSCLC), but they could be detrimental for patients treated with immune checkpoint inhibitors (ICIs). Here, we assessed the association between early use of steroids, clinical outcomes and peripheral immune blood cells modulation in patients with mNSCLC treated with ICIs. We reviewed patients with mNSCLC treated at our institution between April 2013 and December 2017. Early use of steroids was defined as the use of a daily prednisone-equivalent dose ≥10 mg for at least 1 day within 28 days after ICI initiation. Peripheral immune blood cell counts were retrieved at baseline and at 4 and 6 weeks after ICI initiation. Out of 151 patients included, 35 (23%) made early use of steroids that was associated with poor disease control (OR 0.32, p=0.006), progression-free survival (HR 1.80, p=0.003) and overall survival (HR 2.60, p<0.001). Early use of steroids significantly correlated with higher median absolute neutrophil count, neutrophil to lymphocyte ratio (NLR) and derived NLR, and lower median absolute and relative eosinophil count, both at 4 and 6 weeks after ICI initiation. In patients with mNSCLC treated with ICIs, early use of steroids was associated with worse clinical outcomes and remarkable modulation of peripheral blood immune cells, which could contribute to restraining the activation of antitumour immunity. If confirmed in prospective studies, these findings would highlight the importance of carefully evaluating and, whenever possible, avoiding steroids during early phases of ICI treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Steroids are frequently used in patients with metastatic non-small cell lung cancer (mNSCLC), but they could be detrimental for patients treated with immune checkpoint inhibitors (ICIs). Here, we assessed the association between early use of steroids, clinical outcomes and peripheral immune blood cells modulation in patients with mNSCLC treated with ICIs.
METHODS
METHODS
We reviewed patients with mNSCLC treated at our institution between April 2013 and December 2017. Early use of steroids was defined as the use of a daily prednisone-equivalent dose ≥10 mg for at least 1 day within 28 days after ICI initiation. Peripheral immune blood cell counts were retrieved at baseline and at 4 and 6 weeks after ICI initiation.
RESULTS
RESULTS
Out of 151 patients included, 35 (23%) made early use of steroids that was associated with poor disease control (OR 0.32, p=0.006), progression-free survival (HR 1.80, p=0.003) and overall survival (HR 2.60, p<0.001). Early use of steroids significantly correlated with higher median absolute neutrophil count, neutrophil to lymphocyte ratio (NLR) and derived NLR, and lower median absolute and relative eosinophil count, both at 4 and 6 weeks after ICI initiation.
CONCLUSIONS
CONCLUSIONS
In patients with mNSCLC treated with ICIs, early use of steroids was associated with worse clinical outcomes and remarkable modulation of peripheral blood immune cells, which could contribute to restraining the activation of antitumour immunity. If confirmed in prospective studies, these findings would highlight the importance of carefully evaluating and, whenever possible, avoiding steroids during early phases of ICI treatment.
Identifiants
pubmed: 30964126
doi: 10.1136/esmoopen-2018-000457
pii: S2059-7029(20)30189-7
pmc: PMC6435242
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e000457Déclaration de conflit d'intérêts
Competing interests: GLR declares personal fees from Eli Lilly, BMS and AstraZeneca, outside the submitted work. CP declares personal fees from BMS and MSD, outside the submitted work. MCG declares personal fees from MSD, AstraZeneca, Eli Lilly and BMS, outside the submitted work. DS declares personal fees from AstraZeneca, Boehringer Ingelheim and BMS, outside the submitted work.
Références
Cell Mol Life Sci. 2006 Jan;63(1):60-72
pubmed: 16314919
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Mol Cell Endocrinol. 2011 Mar 15;335(1):2-13
pubmed: 20398732
J Clin Invest. 2012 Mar;122(3):787-95
pubmed: 22378047
BJU Int. 2015 Sep;116(3):321-9
pubmed: 24612369
Cell Rep. 2014 May 22;7(4):938-9
pubmed: 24856295
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
N Engl J Med. 2015 Jul 9;373(2):123-35
pubmed: 26028407
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
Lancet. 2016 Apr 9;387(10027):1540-50
pubmed: 26712084
Clin Cancer Res. 2016 Nov 15;22(22):5487-5496
pubmed: 27185375
Cancer Discov. 2016 Aug;6(8):827-37
pubmed: 27301722
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Stem Cell Rev. 2017 Feb;13(1):104-115
pubmed: 27866327
Cell. 2017 Feb 9;168(4):707-723
pubmed: 28187290
Clin Immunol. 2017 Jun;179:66-76
pubmed: 28279811
Lung Cancer. 2017 Apr;106:1-7
pubmed: 28285682
Immunotherapy. 2017 May;9(6):499-506
pubmed: 28472902
J Thorac Oncol. 2017 Aug;12(8):1268-1279
pubmed: 28483607
Clin Genitourin Cancer. 2017 Dec;15(6):678-684.e1
pubmed: 28606735
Eur J Cancer. 2017 Sep;82:56-65
pubmed: 28648699
Lung Cancer. 2017 Sep;111:176-181
pubmed: 28838390
JAMA Oncol. 2018 Mar 1;4(3):374-378
pubmed: 28975219
J Neuroendocrinol. 2018 Feb;30(2):null
pubmed: 29024170
Invest New Drugs. 2018 Aug;36(4):638-646
pubmed: 29159766
Cancer Immunol Immunother. 2018 Mar;67(3):459-470
pubmed: 29204702
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
JAMA Oncol. 2018 Mar 1;4(3):351-357
pubmed: 29327044
Clin Lung Cancer. 2018 May;19(3):280-288.e4
pubmed: 29336998
Cancer Treat Rev. 2018 Mar;64:21-29
pubmed: 29454155
J Cell Physiol. 2018 Oct;233(10):6337-6343
pubmed: 29672849
PLoS One. 2018 Apr 23;13(4):e0195945
pubmed: 29684049
Int J Mol Sci. 2018 May 07;19(5):null
pubmed: 29735917
J Clin Oncol. 2018 Jul 1;36(19):1905-1912
pubmed: 29746230
Clin Lung Cancer. 2018 Sep;19(5):426-434.e1
pubmed: 29803574
J Thorac Oncol. 2018 Nov;13(11):1771-1775
pubmed: 29935305
Cancer Immunol Immunother. 2018 Sep;67(9):1349-1353
pubmed: 29947960
Curr Opin Oncol. 2018 Sep;30(5):345-351
pubmed: 29994900
J Clin Oncol. 2018 Oct 1;36(28):2872-2878
pubmed: 30125216
Target Oncol. 2018 Dec;13(6):795-800
pubmed: 30306460
Science. 1993 Jul 23;261(5120):472-5
pubmed: 8332913
Clin Exp Immunol. 1996 Mar;103(3):482-90
pubmed: 8608650
J Immunol. 1996 Jun 1;156(11):4422-8
pubmed: 8666816
Control Clin Trials. 1996 Aug;17(4):343-6
pubmed: 8889347
Regul Pept. 1998 Jan 2;73(1):59-65
pubmed: 9537674