Journal article

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

Elizabeth Punnoose, Franklin Peale, Edith Szafer-Glusman, Guiyuan Lei, Richard Bourgon, An D Do, Eugene Kim, Liping Zhang, Pedro Farinha, Randy D Gascoyne, F Javier Munoz, Maurizio Martelli, Anja Mottok, Gilles A Salles, Laurie H Sehn, John F Seymour, Marek Trneny, Mikkel Z Oestergaard, Kirsten E Mundt, Umberto Vitolo



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 reprod..

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Funding Acknowledgements

The phase 3 MAIN and GOYA studies, on which this analysis is based, were supported by research funding from F. Hoffmann-La Roche Ltd, Basel, Switzerland. Access to samples from BC Cancer was supported by research funding from F. Hoffmann-La Roche Ltd/Genentech Inc. The authors thank the patients and study investigators who participated in the MAIN and GOYA studies. The authors also thank Chris Bolen (Genentech Inc) for his contribution to data analysis, Mehrdad Mobasher, MD, MPH, for his contribution to the design of the analysis, development of methodology, acquisition of data, analysis and interpretation of data, and study supervision, and Jeffrey Venstrom, MD, for editorial guidance. Under the direction of the authors, editorial assistance was provided by Tara N. Miller and Tara Beers Gibson of Envision Scientific Solutions, and medical writing support was provided by Susan Hasmall and Kate Rijnen of Gardiner-Caldwell Communications, and funded by F. Hoffmann-La Roche Ltd.