Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
03
07
2022
accepted:
18
10
2022
revised:
13
10
2022
pubmed:
6
11
2022
medline:
1
2
2023
entrez:
6
11
2022
Statut:
ppublish
Résumé
Persistence or recurrence of large B-cell lymphoma after CD19-CAR-T is common, yet data guiding management are limited. We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence or progression (1-year cumulative incidence 63% [95%CI: 57-69]). Of 52 post-CAR-T biopsies evaluated by flow cytometry, 49 (94%) expressed CD19. Subsequent anti-cancer treatment was administered in 135/182 (74%) patients with CAR-T treatment failure. Median OS from the first post-CAR-T treatment was 8 months (95%CI 5.6-11.0). Polatuzumab-, standard chemotherapy-, and lenalidomide-based treatments were the most common approaches after CAR-T. No complete responses (CRs) were observed with conventional chemotherapy, while CR rates exceeding 30% were seen following polatuzumab- or lenalidomide-based therapies. Factors associated with poor OS among patients treated post-CAR-T were pre-CAR-T bulky disease (HR 2.27 [1.10-4.72]), lack of response to CAR-T (2.33 [1.02-5.29]), age >65 years (HR 2.65 [1.49-4.73]) and elevated LDH at post-CAR-T treatment (HR 2.95 [1.61-5.38]). The presence of ≥2 of these factors was associated with inferior OS compared to ≤1 (56% vs. 19%). In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may have hold promise.
Identifiants
pubmed: 36335261
doi: 10.1038/s41375-022-01739-2
pii: 10.1038/s41375-022-01739-2
pmc: PMC9892211
mid: NIHMS1845803
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Lenalidomide
F0P408N6V4
Antigens, CD19
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-163Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
N Engl J Med. 2022 Feb 17;386(7):629-639
pubmed: 34904798
Blood. 2021 May 13;137(19):2634-2645
pubmed: 33211842
Lancet. 2020 Sep 19;396(10254):839-852
pubmed: 32888407
Nat Med. 2018 Oct;24(10):1504-1506
pubmed: 30275569
Bone Marrow Transplant. 2016 Jan;51(1):51-7
pubmed: 26367239
Mol Cancer Ther. 2019 Dec;18(12):2246-2257
pubmed: 31395689
Mol Ther. 2021 Feb 3;29(2):636-644
pubmed: 33010231
Cancer Gene Ther. 2015 Oct;22(10):487-95
pubmed: 26450624
Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638
pubmed: 30592986
J Biomed Inform. 2019 Jul;95:103208
pubmed: 31078660
J Clin Oncol. 2020 Nov 10;38(32):3805-3815
pubmed: 33021872
Curr Treat Options Oncol. 2021 Oct 26;22(12):112
pubmed: 34697650
Blood Adv. 2021 Jul 13;5(13):2707-2716
pubmed: 34196677
Biol Blood Marrow Transplant. 2019 Nov;25(11):e344-e351
pubmed: 31279751
J Clin Oncol. 2020 Sep 20;38(27):3119-3128
pubmed: 32401634
J Immunother Cancer. 2020 Mar;8(1):
pubmed: 32152221
Blood. 2019 Apr 11;133(15):1652-1663
pubmed: 30728140
Transplant Cell Ther. 2022 May;28(5):251-257
pubmed: 35218999
Blood. 2019 Aug 15;134(7):626-635
pubmed: 31262783
Nat Rev Cancer. 2021 Mar;21(3):145-161
pubmed: 33483715
J Clin Oncol. 2014 Sep 20;32(27):3059-68
pubmed: 25113753
Lancet Oncol. 2019 Jan;20(1):31-42
pubmed: 30518502
Blood. 2021 Sep 23;138(12):1081-1085
pubmed: 34041526
J Immunother Cancer. 2022 Feb;10(2):
pubmed: 35173030
Blood. 2021 Jan 21;137(3):323-335
pubmed: 32967009
Nat Med. 2022 Apr;28(4):735-742
pubmed: 35314842
Lancet Oncol. 2020 Jul;21(7):978-988
pubmed: 32511983
Lancet Haematol. 2020 Jul;7(7):e511-e522
pubmed: 32589977
N Engl J Med. 2022 Feb 17;386(7):640-654
pubmed: 34891224
N Engl J Med. 2019 Jan 3;380(1):45-56
pubmed: 30501490
Oncoimmunology. 2015 Dec 3;5(4):e1115940
pubmed: 27141398
Lancet Oncol. 2019 Jul;20(7):998-1010
pubmed: 31101489
Br J Haematol. 2020 Jul;190(1):45-51
pubmed: 32135029
Blood Adv. 2020 Nov 24;4(22):5607-5615
pubmed: 33180899
Am J Hematol. 2019 Aug;94(8):E209-E213
pubmed: 31056762
Blood Adv. 2021 Oct 26;5(20):4149-4155
pubmed: 34478487
Leukemia. 2021 Dec;35(12):3383-3393
pubmed: 34002027
Leukemia. 2022 Jan;36(1):189-196
pubmed: 34272481
N Engl J Med. 2017 Dec 28;377(26):2531-2544
pubmed: 29226797
Blood Adv. 2022 May 10;6(9):2757-2762
pubmed: 35240681
Transplant Cell Ther. 2021 Mar;27(3):233-240
pubmed: 33781518
Blood. 2021 Apr 1;137(13):1832-1835
pubmed: 33156925