Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL.
Adenine
/ analogs & derivatives
Aged
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Cyclophosphamide
/ pharmacology
Doxorubicin
/ pharmacology
Female
Humans
Lymphoma, Large B-Cell, Diffuse
/ drug therapy
Male
Middle Aged
Piperidines
/ pharmacology
Prednisone
/ pharmacology
Rituximab
/ pharmacology
Vincristine
/ pharmacology
ABC DLBCL
BTK inhibitor
CD79B
MYD88
NOTCH1
cancer genomics
memory B cell
precision medicine
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
13 12 2021
13 12 2021
Historique:
received:
12
07
2021
revised:
31
08
2021
accepted:
11
10
2021
pubmed:
6
11
2021
medline:
5
1
2022
entrez:
5
11
2021
Statut:
ppublish
Résumé
In diffuse large B cell lymphoma (DLBCL), tumors belonging to the ABC but not GCB gene expression subgroup rely upon chronic active B cell receptor signaling for viability, a dependency that is targetable by ibrutinib. A phase III trial ("Phoenix;" ClinicalTrials.gov: NCT01855750) showed a survival benefit of ibrutinib addition to R-CHOP chemotherapy in younger patients with non-GCB DLBCL, but the molecular basis for this benefit was unclear. Analysis of biopsies from Phoenix trial patients revealed three previously characterized genetic subtypes of DLBCL: MCD, BN2, and N1. The 3-year event-free survival of younger patients (age ≤60 years) treated with ibrutinib plus R-CHOP was 100% in the MCD and N1 subtypes while the survival of patients with these subtypes treated with R-CHOP alone was significantly inferior (42.9% and 50%, respectively). This work provides a mechanistic understanding of the benefit of ibrutinib addition to chemotherapy, supporting its use in younger patients with non-GCB DLBCL.
Identifiants
pubmed: 34739844
pii: S1535-6108(21)00557-2
doi: 10.1016/j.ccell.2021.10.006
pmc: PMC8722194
mid: NIHMS1756296
pii:
doi:
Substances chimiques
Piperidines
0
R-CHOP protocol
0
ibrutinib
1X70OSD4VX
Rituximab
4F4X42SYQ6
Vincristine
5J49Q6B70F
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
Adenine
JAC85A2161
Prednisone
VB0R961HZT
Banques de données
ClinicalTrials.gov
['NCT01855750']
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1643-1653.e3Subventions
Organisme : Intramural NIH HHS
ID : Z01 BC011006
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests L.M.S., G.W., and D.W.H. are inventors on an NIH patent application covering the LymphGen algorithm. L.M.S., G.W., D.W.H., W.H.W., S.B., and B.H. are inventors on an NIH patent application covering the use of BTK inhibitors in genetic subtypes of DLBCL. B.H., S.B., Y.F., J.V., and M.S. are employees of Johnson & Johnson.
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