BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10428077" target="_blank" >RIV/00216208:11110/21:10428077 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/21:10428077

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OB-Vnnf0pe" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OB-Vnnf0pe</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.clml.2020.11.004" target="_blank" >10.1016/j.clml.2020.11.004</a>

Result language

angličtina

Original language name

BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis

Original language description

The prognostic significance of B-cell lymphoma 2 (BCL2) expression in patients with diffuse large B-cell lymphoma (DLBCL) is conflicting. We developed an immunohistochemistry (IHC) algorithm and assay to determine BCL2 expression and assessed the prognostic value of BCL2 in newly diagnosed DLBCL cohorts. BCL2 expression was associated with poorer progression-free survival. Findings support use of our BCL2 IHC scoring system and assay to select BCL2-positive patients for future studies. Introduction: The prognostic value of B-cell lymphoma 2 (BCL2) expression in de novo diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy is of interest to define a target patient population for clinical development of BCL2 inhibitors. We aimed to develop a reproducible immunohistochemistry algorithm and assay to determine BCL2 protein expression and assess the prognostic value of BCL2 in newly diagnosed DLBCL cohorts. Patients and Methods: The prospectively defined algorithm incorporated BCL2 staining intensity and percentage of BCL2-positive cells. Functionally relevant cutoffs were based on the sensitivity of lymphoma cell lines to venetoclax. This assay was highly reproducible across laboratories. The prognostic impact of BCL2 expression was assessed in DLBCL patients from the phase 3 MAIN (n = 230) and GOYA (n = 366) trials, and a population-based registry (n = 310). Results: Approximately 50% of tumors were BCL2 positive, with a higher frequency in high International Prognostic Index (IPI) and activated Bcell-like DLBCL subgroups. BCL2 expression was associated with poorer progression-free survival in the MAIN study (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.81-3.40; multivariate Cox regression adjusted for IPI and cell of origin). This trend was confirmed in the GOYA and registry cohorts in adjusted multivariate analyses (GOYA: HR, 1.72; 95% CI, 1.05-2.82; registry: HR, 1.89; 95% CI, 1.29-2.78). Patients with BCL2 immunohistochemistry-positive and IPIhigh disease had the poorest prognosis: 3-year progression-free survival rates were 51% (GOYA) and 37% (registry). Conclusion: Findings support use of our BCL2 immunohistochemistry scoring system and assay to select patients with BCL2-positive tumors for future studies. (C) 2020 The Authors. Published by Elsevier Inc.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Clinical Lymphoma, Myeloma &amp; Leukemia

ISSN

2152-2650

e-ISSN

—

Volume of the periodical

21

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

22

Pages from-to

267-"278.e10"

UT code for WoS article

000636800200027

EID of the result in the Scopus database

2-s2.0-85097479788