Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia.
Journal
Blood cancer discovery
ISSN: 2643-3249
Titre abrégé: Blood Cancer Discov
Pays: United States
ID NLM: 101764786
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
23
04
2021
revised:
12
07
2021
accepted:
25
08
2021
entrez:
15
11
2021
pubmed:
16
11
2021
medline:
16
11
2021
Statut:
epublish
Résumé
Immune suppression, exhaustion, and senescence are frequently seen throughout disease progression in acute myeloid leukemia (AML). We conducted a phase II study of high-dose cytarabine followed by pembrolizumab 200 mg i.v. on day 14 to examine whether PD-1 inhibition improves clinical responses in relapsed/refractory (R/R) AML. Overall responders could receive pembrolizumab maintenance up to 2 years. Among 37 patients enrolled, the overall response rate, composite complete remission (CRc) rate (primary endpoint), and median overall survival (OS) were 46%, 38%, and 11.1 months, respectively. Patients with refractory/early relapse and those receiving treatment as first salvage had encouraging outcomes (median OS, 13.2 and 11.3 months, respectively). Grade ≥3 immune-related adverse events were rare (14%) and self-limiting. Patients who achieved CRc had a higher frequency of progenitor exhausted CD8 Immune-checkpoint blockade with pembrolizumab was tolerable and feasible after high-dose cytarabine in R/R AML, with encouraging clinical activity, particularly in refractory AML and those receiving treatment as first salvage regimen. Further study of pembrolizumab and other immune-checkpoint blockade strategies after cytotoxic chemotherapy is warranted in AML.
Identifiants
pubmed: 34778801
doi: 10.1158/2643-3230.BCD-21-0070
pii: 2643-3230.BCD-21-0070
pmc: PMC8580622
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Cytarabine
04079A1RDZ
pembrolizumab
DPT0O3T46P
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
616-629Subventions
Organisme : NCI NIH HHS
ID : P50 CA058223
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA247676
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2021 American Association for Cancer Research.
Références
Clin Lymphoma Myeloma Leuk. 2020 Nov;20(11):e871-e882
pubmed: 32792304
J Immunother Cancer. 2015 Jun 16;3:23
pubmed: 26085931
Nat Med. 2020 Sep;26(9):1468-1479
pubmed: 32778827
Cancer Cell. 2020 Sep 14;38(3):380-399.e13
pubmed: 32649887
Cancer Cell. 2014 May 12;25(5):590-604
pubmed: 24794706
Blood. 2011 Nov 10;118(19):5084-95
pubmed: 21881045
Blood. 2015 Jan 1;125(1):133-9
pubmed: 25381062
Eur J Immunol. 2013 Mar;43(3):747-57
pubmed: 23175469
Blood. 2010 Aug 19;116(7):1124-31
pubmed: 20472834
JCI Insight. 2018 Nov 2;3(21):
pubmed: 30385732
Oncologist. 2020 Oct;25(10):878-885
pubmed: 32720734
Cancer Res. 2016 Jan 15;76(2):227-38
pubmed: 26637667
J Hematol Oncol. 2020 Apr 3;13(1):28
pubmed: 32245463
Blood. 2015 Feb 26;125(9):1367-76
pubmed: 25550361
Leuk Res. 1999 Sep;23(9):787-94
pubmed: 10475617
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
Lancet Oncol. 2015 Sep;16(9):1025-1036
pubmed: 26234174
Am J Hematol. 2019 Jan;94(1):111-117
pubmed: 30370956
Blood. 2010 Oct 7;116(14):2484-93
pubmed: 20570856
Blood. 2010 Jan 21;115(3):453-74
pubmed: 19880497
J Clin Oncol. 2012 Jul 10;30(20):2492-9
pubmed: 22585697
N Engl J Med. 2019 Oct 31;381(18):1728-1740
pubmed: 31665578
J Clin Oncol. 2014 Jun 20;32(18):1919-26
pubmed: 24841975
Blood. 2021 Feb 11;137(6):751-762
pubmed: 32929488
J Clin Oncol. 2005 Mar 20;23(9):1969-78
pubmed: 15632409
Immunity. 2019 Jan 15;50(1):195-211.e10
pubmed: 30635237
Blood. 2010 Aug 5;116(5):788-92
pubmed: 20442368
Haematologica. 2015 Oct;100(10):e409-11
pubmed: 26160876
Eur J Haematol. 2008 Feb;80(2):115-26
pubmed: 18076637
Immunity. 2019 Jan 15;50(1):181-194.e6
pubmed: 30635236
F1000Res. 2017 May 26;6:748
pubmed: 28663787
Cancer. 2019 May 1;125(9):1470-1481
pubmed: 30500073
Nat Immunol. 2020 Dec;21(12):1552-1562
pubmed: 33046887
Br J Haematol. 2003 Jun;121(5):692-702
pubmed: 12780783
Cancer Discov. 2019 Mar;9(3):370-383
pubmed: 30409776
Blood. 2011 Jan 13;117(2):608-17
pubmed: 20935254
Blood. 2017 Aug 10;130(6):722-731
pubmed: 28588020
Commun Biol. 2019 May 14;2:183
pubmed: 31098416
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Blood Adv. 2020 Oct 27;4(20):5011-5024
pubmed: 33057635
Eur J Haematol. 2014 Mar;92(3):195-203
pubmed: 24175978
Nature. 2019 Dec;576(7787):465-470
pubmed: 31827286
Lancet Haematol. 2019 Sep;6(9):e480-e488
pubmed: 31400961
Sci Transl Med. 2020 Jun 3;12(546):
pubmed: 32493790
N Engl J Med. 2018 Jun 21;378(25):2386-2398
pubmed: 29860938
J Clin Oncol. 2017 Mar;35(7):709-717
pubmed: 27646942
Blood. 1996 Jul 15;88(2):756
pubmed: 8695828
Blood. 2010 Dec 23;116(26):5818-23; quiz 6153
pubmed: 20923968
Clin Cancer Res. 2019 Jul 15;25(14):4231-4237
pubmed: 30992301
JAMA Oncol. 2020 Dec 1;6(12):1890-1899
pubmed: 33030517
Cancer Immunol Immunother. 2010 Dec;59(12):1839-49
pubmed: 20814675