Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL coexpressing BCL2 and MYC in the phase 3 PHOENIX trial.
Blood Adv
; 7(10): 2008-2017, 2023 05 23.
Article
en En
| MEDLINE
| ID: mdl-36696540
ABSTRACT
Diffuse large B-cell lymphoma (DLBCL), with high coexpression of BCL2 and MYC proteins (DE lymphoma), is considered an adverse prognostic indicator associated mostly with non-germinal center B-cell-like (non-GCB) DLBCL. BCL2/MYC overexpression is associated with B-cell receptor (BCR) pathway activation; consequently, DE DLBCL may be sensitive to BCR inhibitors. We assessed whether high BCL2/MYC coexpression by RNA sequencing could identify a patient subset responsive to ibrutinib using baseline biopsies from the PHOENIX trial, which evaluated the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-GCB DLBCL. BCL2/MYC RNA expression was correlated with lower event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimates with Cox regression and log-rank testing. In total, 234 of 766 (30.5%) patients had high BCL2/MYC coexpression 123 of 386 (31.9%) received ibrutinib plus R-CHOP and 111 of 380 (29.2%) received R-CHOP. EFS was superior with ibrutinib plus R-CHOP compared with R-CHOP alone in patients with high BCL2/MYC coexpression, but there was no significant impact on OS. However, EFS and OS showed clinically meaningful improvement with ibrutinib plus R-CHOP over R-CHOP alone in patients aged <60 years with high BCL2/MYC coexpression. We observed a significant association between high BCL2/MYC coexpression and activated B-cell-like and MYD88L265P/CD79B-mutated subtypes of DLBCL. Consequently, high BCL2/MYC coexpression identified a subset of non-GCB DLBCL that may be preferentially responsive to ibrutinib and warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT01855750.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas c-myc
/
Linfoma de Células B Grandes Difuso
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Blood Adv
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido