BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
33303421
DOI
10.1016/j.clml.2020.11.004
PII: S2152-2650(20)30628-5
Knihovny.cz E-zdroje
- Klíčová slova
- ABC DLBCL subtype, Biomarkers, Cell of origin, GCB DLBCL subtype, Immunohistochemistry,
- MeSH
- chemorezistence genetika MeSH
- difúzní velkobuněčný B-lymfom farmakoterapie genetika mortalita patologie MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- Kaplanův-Meierův odhad MeSH
- klinické zkoušky, fáze III jako téma MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- multicentrické studie jako téma MeSH
- nádorové biomarkery analýza genetika MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie farmakologie terapeutické užití MeSH
- protoonkogenní proteiny c-bcl-2 analýza genetika MeSH
- randomizované kontrolované studie jako téma MeSH
- registrace statistika a číselné údaje MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- BCL2 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- protoonkogenní proteiny c-bcl-2 MeSH
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 B-cell-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 IPI-high 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.
Center for Lymphoid Cancer British Columbia Cancer Vancouver British Columbia Canada
Department of Hematology General Hospital Charles University Prague Czech Republic
Department of Hematology Hospices Civils de Lyon Université de Lyon Pierre Bénite France
Department of Translational and Precision Medicine Hematology Section Sapienza University Rome Italy
F Hoffmann La Roche Ltd Basel Switzerland
Genentech Inc South San Francisco CA
Roche Products Limited Welwyn Garden City England United Kingdom
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