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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00064165:_____/21:10428077

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Clinical Lymphoma, Myeloma &amp; Leukemia

ISSN

2152-2650

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

22

Strana od-do

267-"278.e10"

Kód UT WoS článku

000636800200027

EID výsledku v databázi Scopus

2-s2.0-85097479788