Checkpoint Inhibitors.
Journal
Deutsches Arzteblatt international
ISSN: 1866-0452
Titre abrégé: Dtsch Arztebl Int
Pays: Germany
ID NLM: 101475967
Informations de publication
Date de publication:
22 02 2019
22 02 2019
Historique:
received:
05
05
2018
revised:
05
05
2018
accepted:
06
12
2018
entrez:
4
4
2019
pubmed:
4
4
2019
medline:
15
4
2020
Statut:
ppublish
Résumé
Treatment with checkpoint inhibitors such as anti-programmed death-1 (anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibodies can prolong the survival of cancer patients, but it also induces autoimmune side effects in 86-96% of patients by activating the immune system. In 17-59% of patients, these are severe or even life-threatening. This review is based on pertinent articles retrieved by a search in PubMed and on an evaluation of a side-effect registry. Checkpoint-inhibitor-induced autoimmune side effects manifest themselves in all organ systems, most commonly as skin lesions (46-62%), autoimmune colitis (22-48%), autoimmune hepatitis (7-33%), and endocrinopathies (thyroiditis, hypophysitis, adrenalitis, diabetes mellitus; 12-34%). Rarer side effects include pneumonitis (3-8%), nephritis (1-7%), cardiac side effects including cardiomyositis (5%), and neurological side effects (1-5%). Severe (sometimes lethal) side effects arise in 17-21%, 20-28%, and 59% of patients undergoing anti-PD-1 and anti- CTLA-4 antibody treatment and the approved combination therapy, respectively. With proper monitoring, however, these side effects can be recognized early and, usually, treated with success. Endocrine side effects generally require long-term hormone substitution. Patients who have stopped taking checkpoint inhibitors because of side effects do not show a poorer response of their melanoma or shorter survival in comparison to patients who continue to take checkpoint inhibitors. The complex management of checkpoint-inhibitor-induced side effects should be coordinated in experienced centers. The creation of an interdisciplinary "tox team" with designated experts for organ-specific side effects has proven useful. Prospective registry studies based on structured documentation of side effects in routine clinical practice are currently lacking and urgently needed.
Sections du résumé
BACKGROUND
Treatment with checkpoint inhibitors such as anti-programmed death-1 (anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibodies can prolong the survival of cancer patients, but it also induces autoimmune side effects in 86-96% of patients by activating the immune system. In 17-59% of patients, these are severe or even life-threatening.
METHODS
This review is based on pertinent articles retrieved by a search in PubMed and on an evaluation of a side-effect registry.
RESULTS
Checkpoint-inhibitor-induced autoimmune side effects manifest themselves in all organ systems, most commonly as skin lesions (46-62%), autoimmune colitis (22-48%), autoimmune hepatitis (7-33%), and endocrinopathies (thyroiditis, hypophysitis, adrenalitis, diabetes mellitus; 12-34%). Rarer side effects include pneumonitis (3-8%), nephritis (1-7%), cardiac side effects including cardiomyositis (5%), and neurological side effects (1-5%). Severe (sometimes lethal) side effects arise in 17-21%, 20-28%, and 59% of patients undergoing anti-PD-1 and anti- CTLA-4 antibody treatment and the approved combination therapy, respectively. With proper monitoring, however, these side effects can be recognized early and, usually, treated with success. Endocrine side effects generally require long-term hormone substitution. Patients who have stopped taking checkpoint inhibitors because of side effects do not show a poorer response of their melanoma or shorter survival in comparison to patients who continue to take checkpoint inhibitors.
CONCLUSION
The complex management of checkpoint-inhibitor-induced side effects should be coordinated in experienced centers. The creation of an interdisciplinary "tox team" with designated experts for organ-specific side effects has proven useful. Prospective registry studies based on structured documentation of side effects in routine clinical practice are currently lacking and urgently needed.
Identifiants
pubmed: 30940340
pii: arztebl.2019.0119
doi: 10.3238/arztebl.2019.0119
pmc: PMC6454802
doi:
pii:
Substances chimiques
Antineoplastic Agents, Immunological
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
119-126Commentaires et corrections
Type : CommentIn
Références
Case Rep Oncol Med. 2015;2015:794842
pubmed: 25918658
J Immunother. 2007 Nov-Dec;30(8):825-30
pubmed: 18049334
Cornea. 2016 Mar;35(3):399-401
pubmed: 26771550
Eur J Cancer. 2018 Nov;104:137-144
pubmed: 30347289
Neuro Oncol. 2014 Apr;16(4):589-93
pubmed: 24482447
Cardiology. 2017;136(1):49-51
pubmed: 27554835
Eur J Cancer. 2016 Jun;60:12-25
pubmed: 27043866
Lancet. 2018 Mar 10;391(10124):933
pubmed: 29536852
J Am Coll Cardiol. 2018 Apr 24;71(16):1755-1764
pubmed: 29567210
Cancer Immunol Immunother. 2018 Apr;67(4):563-573
pubmed: 29289977
N Engl J Med. 2018 Mar 22;378(12):1164
pubmed: 29565520
Case Rep Med. 2017;2017:1093858
pubmed: 29312452
J Cutan Pathol. 2016 Sep;43(9):787-91
pubmed: 27161449
Lancet Oncol. 2018 Nov;19(11):1468-1479
pubmed: 30262187
Tohoku J Exp Med. 2016;239(2):155-8
pubmed: 27297738
JAMA Dermatol. 2017 Jul 1;153(7):721-722
pubmed: 28467548
Case Rep Oncol. 2017 May 24;10(2):473-478
pubmed: 28626408
J Immunother Cancer. 2016 Jun 21;4:36
pubmed: 27330809
J Clin Oncol. 2011 Mar 20;29(9):e237-40
pubmed: 21220617
Ann Intern Med. 2017 Nov 7;167(9):683-684
pubmed: 28869988
Cancer Treat Rev. 2016 Mar;44:51-60
pubmed: 26874776
J Oncol Pharm Pract. 2019 Jan;25(1):221-225
pubmed: 28825374
J Immunother Cancer. 2015 Feb 17;3:4
pubmed: 25705383
J Clin Oncol. 2015 Oct 1;33(28):3193-8
pubmed: 26282644
J Immunother Cancer. 2016 Aug 16;4:50
pubmed: 27532025
Front Immunol. 2018 Jan 30;9:108
pubmed: 29441072
Ann Rheum Dis. 2017 Jan;76(1):43-50
pubmed: 27307501
Lancet. 2017 Jun 24;389(10088):2492-2502
pubmed: 28434648
United European Gastroenterol J. 2018 Aug;6(7):970-973
pubmed: 30228883
J Oncol Pharm Pract. 2017 Dec;23(8):620-624
pubmed: 27590328
Clin Infect Dis. 2016 Dec 1;63(11):1490-1493
pubmed: 27501841
Hematol Oncol. 2017 Dec;35(4):875-877
pubmed: 27539158
J Infect Dis. 2017 Jun 1;215(11):1725-1733
pubmed: 28431010
Eur J Cancer. 2017 Mar;73:1-8
pubmed: 28064139
Mult Scler. 2015 Apr;21(5):670
pubmed: 25257614
Cancer Immunol Res. 2016 May;4(5):383-9
pubmed: 26928461
Am J Med Sci. 2015 Dec;350(6):512-3
pubmed: 26488944
Arthritis Rheumatol. 2014 Mar;66(3):768-9
pubmed: 24574239
Lancet Oncol. 2017 Sep;18(9):1202-1210
pubmed: 28729151
Target Oncol. 2016 Aug;11(4):553-6
pubmed: 26940583
Curr Opin Oncol. 2017 Mar;29(2):136-144
pubmed: 28059853
J Immunother Cancer. 2016 Oct 18;4:66
pubmed: 27777775
Lancet. 2017 Oct 21;390(10105):1853-1862
pubmed: 28822576
Lancet Oncol. 2015 Apr;16(4):375-84
pubmed: 25795410
Pediatr Blood Cancer. 2017 Dec;64(12):
pubmed: 28643391
Am J Kidney Dis. 2016 Aug;68(2):287-291
pubmed: 27113507
J Immunother. 2015 Jun;38(5):212-5
pubmed: 25962110
Eur J Cancer. 2016 Nov;67:66-72
pubmed: 27614165
J Immunother Cancer. 2015 Apr 21;3:11
pubmed: 25901283
Nat Rev Clin Oncol. 2016 Aug;13(8):473-86
pubmed: 27141885
Clin Cancer Res. 2016 Aug 15;22(16):4023-9
pubmed: 26957557
J Clin Oncol. 2018 Jun 10;36(17):1714-1768
pubmed: 29442540
Transfus Med Hemother. 2017 Nov;44(6):426-428
pubmed: 29344020
J Oncol Pharm Pract. 2016 Jun;22(3):537-42
pubmed: 25712627
J Immunother Cancer. 2017 Jul 18;5(1):54
pubmed: 28716137
Oncologist. 2017 Jun;22(6):709-718
pubmed: 28495807
Arthritis Rheumatol. 2016 Feb;68(2):556-7
pubmed: 26314277
Cancer Treat Rev. 2017 Jun;57:36-49
pubmed: 28550712
Cancer Immunol Res. 2017 Dec;5(12):1133-1140
pubmed: 29079654
N Engl J Med. 2016 Nov 03;375(18):1749-1755
pubmed: 27806233
Eur J Cancer. 2016 Feb;54:139-148
pubmed: 26765102
Clin Cancer Res. 2015 Feb 15;21(4):749-55
pubmed: 25538262
JAMA Dermatol. 2015 Feb;151(2):195-9
pubmed: 25321335
J Clin Oncol. 2016 Sep 1;34(25):2969-79
pubmed: 27354481
Cancer Immunol Immunother. 2015 Jun;64(6):765-7
pubmed: 25828465
J Oncol Pharm Pract. 2017 Apr;23(3):231-234
pubmed: 26946531
JAMA Oncol. 2016 Feb;2(2):234-40
pubmed: 26633184
Ann Rheum Dis. 2017 Dec;76(12):2061-2064
pubmed: 28830882
Scientifica (Cairo). 2013;2013:857519
pubmed: 24278787
Lung Cancer. 2016 Sep;99:123-6
pubmed: 27565926
J Cutan Pathol. 2016 Aug;43(8):688-96
pubmed: 27086658
J Immunother Cancer. 2017 Jan 18;5:7
pubmed: 28116090
Lancet Oncol. 2016 Oct;17(10):1374-1385
pubmed: 27592805
Cancer Immunol Res. 2015 Dec;3(12):1299-302
pubmed: 26419960
J Immunother Cancer. 2016 Oct 18;4:64
pubmed: 27777773
Ann Oncol. 2017 Feb 1;28(2):368-376
pubmed: 27687304
Eur J Cancer. 2016 Jun;60:210-25
pubmed: 27084345
J Immunother Cancer. 2017 Dec 19;5(1):97
pubmed: 29254501
Ann Oncol. 2017 Feb 1;28(2):377-385
pubmed: 28426103
Oncologist. 2017 Jun;22(6):749-753
pubmed: 28559410
Lancet. 2017 Jan 21;389(10066):255-265
pubmed: 27979383
Cancer Treat Rev. 2016 Apr;45:7-18
pubmed: 26922661
Intern Med. 2018 May 1;57(9):1259-1263
pubmed: 29279511
Clin Cancer Res. 2016 Dec 15;22(24):6051-6060
pubmed: 27535979
J Immunother. 2015 Feb-Mar;38(2):77-9
pubmed: 25658617
ESMO Open. 2017 Oct 10;2(4):e000268
pubmed: 29081991
Eur J Cancer. 2017 Sep;82:128-136
pubmed: 28666240
JAMA Neurol. 2016 Aug 1;73(8):928-33
pubmed: 27271951
Nat Commun. 2016 Feb 02;7:10391
pubmed: 26837003
N Engl J Med. 2016 Nov 10;375(19):1845-1855
pubmed: 27717298
J Immunother. 2018 Apr;41(3):164-167
pubmed: 29309291
Eur J Cancer. 2016 Feb;54:172-174
pubmed: 26687374
Autoimmun Rev. 2018 Mar;17(3):284-289
pubmed: 29341936
J Clin Oncol. 2020 Feb 20;38(6):567-575
pubmed: 31880964
J Diabetes Investig. 2016 Nov;7(6):915-918
pubmed: 27181090
Endoscopy. 2012;44 Suppl 2 UCTN:E78-9
pubmed: 22396291
J Clin Oncol. 2017 Dec 1;35(34):3807-3814
pubmed: 28841387
J Immunother. 2016 Nov/Dec;39(9):379-382
pubmed: 27662340
Ann Rheum Dis. 2017 Oct;76(10):1747-1750
pubmed: 28600350
Eur J Cancer. 2016 Jun;60:190-209
pubmed: 27085692
Diabetes Care. 2015 Apr;38(4):e55-7
pubmed: 25805871
Case Rep Oncol. 2016 Nov 7;9(3):691-697
pubmed: 27920704
Ann Dermatol Venereol. 2016 Dec;143(12):881-882
pubmed: 27692689
JAAD Case Rep. 2016 Jul 14;2(3):264-8
pubmed: 27486590
Lung Cancer. 2016 Sep;99:117-9
pubmed: 27565924
Diabetes Care. 2015 Nov;38(11):e182-3
pubmed: 26310693
N Engl J Med. 2017 Oct 5;377(14):1345-1356
pubmed: 28889792
PLoS One. 2013;8(1):e53745
pubmed: 23341990
N Engl J Med. 2018 Jan 11;378(2):158-168
pubmed: 29320654
J Neurol Sci. 2014 Sep 15;344(1-2):229-31
pubmed: 24980937
BMJ Case Rep. 2016 Jul 20;2016:
pubmed: 27440853
Future Oncol. 2015;11(17):2471-84
pubmed: 26274495
J Immunother Cancer. 2017 Jan 17;5:3
pubmed: 28105370
ESMO Open. 2018 Jan 13;3(1):e000278
pubmed: 29387476
JAAD Case Rep. 2016 Aug 17;2(4):343-5
pubmed: 27570820
Eur J Endocrinol. 2018 Feb;178(2):173-180
pubmed: 29187509
JAMA Oncol. 2016 Dec 01;2(12):1607-1616
pubmed: 27540850
Sci Transl Med. 2014 Apr 2;6(230):230ra45
pubmed: 24695685
J Immunother. 2015 Jan;38(1):37-9
pubmed: 25415286
BMC Nephrol. 2016 Nov 22;17(1):188
pubmed: 27876011
Melanoma Manag. 2015 Nov;2(4):311-314
pubmed: 30190859
Eur J Cancer. 2017 Apr;75:24-32
pubmed: 28214654
Oncol Res Treat. 2014;37(12):757-60
pubmed: 25531722
Lancet Oncol. 2018 Jun;19(6):e327
pubmed: 29893264
J Immunother. 2017 Sep;40(7):286-288
pubmed: 28604555
J Hepatol. 2018 Jun;68(6):1181-1190
pubmed: 29427729
Ann Oncol. 2017 Jun 01;28(6):1368-1379
pubmed: 28368458
Kidney Int. 2016 Sep;90(3):638-47
pubmed: 27282937
JAMA Dermatol. 2015 Jul;151(7):797-9
pubmed: 25875052
Lancet Oncol. 2017 Sep;18(9):1182-1191
pubmed: 28734759
J Immunother. 2017 Nov/Dec;40(9):341-344
pubmed: 29028789
Eur J Cancer. 2017 Aug;81:203-205
pubmed: 28641200
Cancer Immunol Res. 2015 Jun;3(6):598-601
pubmed: 25922203
Oncoimmunology. 2016 Feb 18;5(6):e1128611
pubmed: 27471608
Curr Opin Oncol. 2016 Jul;28(4):254-63
pubmed: 27136138
Anticancer Drugs. 2017 Aug;28(7):811-814
pubmed: 28574922
J Immunother Cancer. 2017 Feb 21;5:8
pubmed: 28239462
Clin Toxicol (Phila). 2018 Jul;56(7):667-671
pubmed: 29126352
J Clin Oncol. 2017 Mar;35(7):709-717
pubmed: 27646942
Ann Oncol. 2017 Dec 1;28(12):3104-3106
pubmed: 28950303
J Immunother. 2018 Jan;41(1):35-38
pubmed: 29077601
JAMA Oncol. 2018 Feb 01;4(2):173-182
pubmed: 28973656
J Clin Oncol. 2012 Nov 20;30(33):e356-7
pubmed: 23045571
BMC Res Notes. 2015 Jul 26;8:316
pubmed: 26209970
Oncol Res Treat. 2014;37(6):351-3
pubmed: 24903767
BMJ Case Rep. 2016 Mar 23;2016:
pubmed: 27009198
N Engl J Med. 2013 Jul 11;369(2):134-44
pubmed: 23724846
J Am Acad Dermatol. 2016 Mar;74(3):455-61.e1
pubmed: 26793994
J Cutan Pathol. 2017 Dec;44(12):1080-1086
pubmed: 28901560
Melanoma Res. 2015 Jun;25(3):265-8
pubmed: 25831416
N Engl J Med. 2009 Jul 9;361(2):211-2
pubmed: 19587352
J Eur Acad Dermatol Venereol. 2017 May;31(5):e254-e257
pubmed: 27739129
Ann Oncol. 2017 Jul 1;28(suppl_4):iv119-iv142
pubmed: 28881921
Br J Dermatol. 2017 Apr;176(4):1060-1063
pubmed: 27291635
J Immunother. 2017 Sep;40(7):277-281
pubmed: 28719552