Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL coexpressing BCL2 and MYC in the phase 3 PHOENIX trial.

Autor:	Johnson PWM; Centre for Cancer Immunology, University of Southampton, Southampton General Hospital, Southampton, United Kingdom., Balasubramanian S; Oncology Translational Research, Janssen Research & Development, San Diego, CA., Hodkinson B; Oncology Translational Research, Janssen Research & Development, Spring House, PA., Shreeve SM; Clinical Oncology, Janssen Research & Development, San Diego, CA., Sun S; Oncology Translational Research, Janssen Research & Development, Spring House, PA., Srinivasan S; Oncology Translational Research, Janssen Research & Development, Lower Gwynedd Township, PA., Steele AJ; Oncology Translational Research, Janssen Research & Development, Spring House, PA., Vermeulen J; Clinical Oncology, Janssen Research & Development, Leiden, The Netherlands., Sehn LH; British Columbia Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver, BC, Canada., Wilson WH; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 May 23; Vol. 7 (10), pp. 2008-2017.
DOI:	10.1182/bloodadvances.2022009389
Abstrakt:	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. (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)
Databáze:	MEDLINE
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