Factors associated with long-term outcomes of CD19 CAR T-cell therapy for relapsed/refractory CLL.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
accepted:
23
09
2023
received:
07
08
2023
medline:
20
11
2023
pubmed:
29
9
2023
entrez:
29
9
2023
Statut:
ppublish
Résumé
High response rates have been reported after CD19-targeted chimeric antigen receptor-modified (CD19 CAR) T-cell therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), yet the factors associated with duration of response in this setting are poorly characterized. We analyzed long-term outcomes in 47 patients with R/R CLL and/or Richter transformation treated on our phase 1/2 clinical trial of CD19 CAR T-cell therapy with an updated median follow-up of 79.6 months. Median progression-free survival (PFS) was 8.9 months, and the 6-year PFS was 17.8%. Maximum standardized uptake value (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.07-1.23; P < .001) and bulky disease (≥5 cm; HR, 2.12; 95% CI, 1.06-4.26; P = .034) before lymphodepletion were associated with shorter PFS. Day +28 complete response by positron emission tomography-computed tomography (HR, 0.13; 95% CI, 0.04-0.40; P < .001), day +28 measurable residual disease (MRD) negativity by multiparameter flow cytometry (HR, 0.08; 95% CI, 0.03-0.22; P < .001), day +28 MRD negativity by next-generation sequencing (HR, 0.21; 95% CI, 0.08-0.51; P < .001), higher peak CD8+ CAR T-cell expansion (HR, 0.49; 95% CI; 0.36-0.68; P < .001), higher peak CD4+ CAR T-cell expansion (HR, 0.47; 95% CI; 0.33-0.69; P < .001), and longer CAR T-cell persistence (HR, 0.56; 95% CI, 0.44-0.72; P < .001) were associated with longer PFS. The 6-year duration of response and overall survival were 26.4% and 31.2%, respectively. CD19 CAR T-cell therapy achieved durable responses with curative potential in a subset of patients with R/R CLL. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
Identifiants
pubmed: 37774014
pii: 498171
doi: 10.1182/bloodadvances.2023011399
pmc: PMC10690558
doi:
Substances chimiques
Antigens, CD19
0
Receptors, Antigen, T-Cell
0
Receptors, Chimeric Antigen
0
Banques de données
ClinicalTrials.gov
['NCT01865617']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6990-7005Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL007093
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92019D00018
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056465
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136551
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197734
Pays : United States
Informations de copyright
© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
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