Chimeric Antigen Receptor T Cells as Salvage Therapy for Post-Chimeric Antigen Receptor T Cell Failure.
Acute lymphoblastic leukemia
Chimeric antigen receptor T cells
Immunotherapy
Relapse
Salvage therapy
Journal
Transplantation and cellular therapy
ISSN: 2666-6367
Titre abrégé: Transplant Cell Ther
Pays: United States
ID NLM: 101774629
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
01
05
2023
revised:
09
06
2023
accepted:
28
06
2023
pmc-release:
01
09
2024
medline:
28
8
2023
pubmed:
3
7
2023
entrez:
2
7
2023
Statut:
ppublish
Résumé
Outcomes for post-chimeric antigen receptor (CAR) T cell therapy (CART) relapse are poor. The utilization of a unique CAR T cell construct for post-CART failure is increasing, but this approach is not well described. In this study, with CART-A the first unique CAR T cell construct received and CART-B the second, the primary objective was to characterize outcomes following CART-B. Secondary objectives included evaluating safety and toxicity with sequential CART infusions; investigating the impact of potential factors, such as antigen modulation and interval therapy, on CART-B response; and characterizing long-term outcomes in patients receiving multiple CARTs. This was a retrospective review (NCT03827343) of children and young adults with B cell acute lymphoblastic leukemia (B-ALL) undergoing CART therapy who received at least 2 unique CART constructs, excluding interim CART reinfusions of the same product. Of 135 patients, 61 (45.1%) received 2 unique CART constructs, including 13 who received >2 CARTs over time. Patients included in this analysis received 14 distinct CARTs targeting CD19 and/or CD22. The median age at CART-A was 12.6 years (range, 3.3 to 30.4 years). The median time from CART-A to CART-B was 302 days (range, 53 to 1183 days). CART-B targeted a different antigen than CART-A in 48 patients (78.7%), owing primarily to loss of CART-A antigen target. The rate of complete remission (CR) was lower with CART-B (65.5%; 40 of 61) than with CART-A (88.5%; 54 of 61; P = .0043); 35 of 40 (87.5%) CART-B responders had CART-B targeting a different antigen than CART-A. Among the 21 patients with a partial response or nonresponse to CART-B, 8 (38.1%) received CART-B with the same antigen target as CART-A. Of 40 patients with CART-B complete response (CR), 29 (72.5%) relapsed. For the 21 patients with evaluable data, the relapse immunophenotype was antigen
Identifiants
pubmed: 37394115
pii: S2666-6367(23)01378-7
doi: 10.1016/j.jtct.2023.06.019
pmc: PMC10529970
mid: NIHMS1913678
pii:
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Banques de données
ClinicalTrials.gov
['NCT03827343']
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
574.e1-574.e10Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC011823
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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