Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor-induced colitis.
Aged
Antibodies, Monoclonal
/ adverse effects
Antineoplastic Agents, Immunological
/ adverse effects
CTLA-4 Antigen
/ antagonists & inhibitors
Colitis
/ chemically induced
Female
Humans
Immune Checkpoint Inhibitors
/ adverse effects
Lymphocytes
/ drug effects
Male
Melanoma
/ complications
Middle Aged
Neutrophils
/ drug effects
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Vitamin D
/ administration & dosage
colitis
immunotherapy
irAE
melanoma
toxicity
vitamin D
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
received:
14
02
2020
revised:
24
04
2020
accepted:
27
04
2020
pubmed:
23
6
2020
medline:
19
5
2021
entrez:
23
6
2020
Statut:
ppublish
Résumé
There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.
Sections du résumé
BACKGROUND
There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis.
METHODS
We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital.
RESULTS
The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort.
CONCLUSIONS
This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.
Identifiants
pubmed: 32567084
doi: 10.1002/cncr.32966
pmc: PMC7381363
mid: NIHMS1601216
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
CTLA-4 Antigen
0
CTLA4 protein, human
0
Immune Checkpoint Inhibitors
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Vitamin D
1406-16-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3758-3767Subventions
Organisme : Massachusetts General Hospital
ID : 2T32CA071345-21A1
Organisme : NIDDK NIH HHS
ID : 1K08 DK114563-01
Pays : United States
Organisme : Parker Institute for Cancer Immunotherapy
ID : 5812101
Organisme : American Gastroenterological Association
Organisme : NIDDK NIH HHS
ID : K08 DK114563
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA071345
Pays : United States
Informations de copyright
© 2020 American Cancer Society.
Références
PLoS One. 2019 Mar 7;14(3):e0213505
pubmed: 30845259
J Immunother Cancer. 2015 Sep 15;3:39
pubmed: 26380086
Clin Cancer Res. 2019 Aug 1;25(15):4616-4623
pubmed: 31043390
Trends Immunol. 2019 Jun;40(6):511-523
pubmed: 31053497
Ann Oncol. 2017 Feb 1;28(2):368-376
pubmed: 27687304
Bone Marrow Transplant. 2015 Sep;50(9):1217-23
pubmed: 26030049
Ann Oncol. 2017 Oct 1;28(10):2377-2385
pubmed: 28945858
Nat Immunol. 2013 Dec;14(12):1212-8
pubmed: 24240160
J Crohns Colitis. 2016 Apr;10(4):395-401
pubmed: 26783344
Saudi J Gastroenterol. 2011 May-Jun;17(3):194-8
pubmed: 21546723
Mol Cell Biol. 2011 Sep;31(17):3653-69
pubmed: 21746882
J Neuroinflammation. 2011 May 24;8:56
pubmed: 21605467
Medicine (Baltimore). 2018 Nov;97(46):e12662
pubmed: 30431562
Nutr J. 2019 Mar 11;18(1):16
pubmed: 30871542
Mayo Clin Proc. 2006 Nov;81(11):1462-71
pubmed: 17120402
Sci Rep. 2019 Oct 1;9(1):14039
pubmed: 31575933
J Clin Lab Anal. 2013 Jan;27(1):72-6
pubmed: 23292894
Ann Intern Med. 2012 Mar 6;156(5):350-9
pubmed: 22393130
Clin Rev Allergy Immunol. 2013 Oct;45(2):217-26
pubmed: 23359064
J Immunother. 2018 Apr;41(3):101-108
pubmed: 29401166
Handb Exp Pharmacol. 2009;(188):251-73
pubmed: 19031030
Clin Cancer Res. 2016 Dec 1;22(23):5673-5681
pubmed: 27358490
Am J Clin Oncol. 2016 Feb;39(1):98-106
pubmed: 26558876
Aliment Pharmacol Ther. 2011 Sep;34(6):649-55
pubmed: 21790683
Am J Physiol Gastrointest Liver Physiol. 2015 Sep 1;309(5):G341-9
pubmed: 26159695
Dig Liver Dis. 2017 Feb;49(2):170-174
pubmed: 27903418
J Clin Oncol. 2017 Mar;35(7):785-792
pubmed: 28068177
Gut. 2000 Aug;47(2):211-4
pubmed: 10896912
JAMA Oncol. 2016 Feb;2(2):234-40
pubmed: 26633184
ACG Case Rep J. 2017 Oct 11;4:e112
pubmed: 29043290
Ann Oncol. 2017 Jun 1;28(6):1368-1379
pubmed: 28368458
J Clin Invest. 2013 Sep;123(9):3983-96
pubmed: 23945234
Cancer. 2018 Sep 15;124(18):3706-3714
pubmed: 29975414
Science. 2013 Dec 20;342(6165):1432-3
pubmed: 24357284
Gastroenterology. 2012 Mar;142(3):482-9
pubmed: 22155183
Clin Gastroenterol Hepatol. 2017 Feb;15(2):240-246.e1
pubmed: 27266980
N Engl J Med. 2015 May 21;372(21):2006-17
pubmed: 25891304
Gut. 2018 Nov;67(11):2056-2067
pubmed: 30131322
Front Immunol. 2017 Jan 20;7:697
pubmed: 28163705
Gastroenterology. 2018 Oct;155(4):1079-1089.e3
pubmed: 29958857
Cancer Immunol Immunother. 2018 May;67(5):825-834
pubmed: 29487980
World J Gastroenterol. 2017 Sep 7;23(33):6137-6146
pubmed: 28970729
Oncoimmunology. 2017 Jul 5;6(10):e1344805
pubmed: 29123955
Nat Clin Pract Rheumatol. 2008 Aug;4(8):404-12
pubmed: 18594491
J Clin Gastroenterol. 2019 Nov/Dec;53(10):e409-e415
pubmed: 31356558
Gastroenterology. 2019 Sep;157(3):647-659.e4
pubmed: 31014995
Nutrients. 2015 Apr 22;7(4):3011-21
pubmed: 25912039
Front Immunol. 2017 Nov 15;8:1547
pubmed: 29230210
Oncol Lett. 2017 Nov;14(5):5671-5680
pubmed: 29113194
Digestion. 2017;95(3):188-193
pubmed: 28288458
N Engl J Med. 2018 Jan 11;378(2):158-168
pubmed: 29320654
J Clin Oncol. 2012 Jul 20;30(21):2691-7
pubmed: 22614989
J Clin Oncol. 2020 Feb 20;38(6):576-583
pubmed: 31800340
Science. 2006 Mar 24;311(5768):1770-3
pubmed: 16497887
Gastroenterology. 2005 Sep;129(3):827-36
pubmed: 16143122
Bratisl Lek Listy. 2015;116(4):213-7
pubmed: 25773946
Immunotherapy. 2016 May;8(5):583-600
pubmed: 27140411