T Petrella1, C Copie-Bergman2, J Brière3, R Delarue4, F Jardin5, P Ruminy5, C Thieblemont6, M Figeac7, D Canioni3, P Feugier8, B Fabiani9, K Leroy2, M Parrens10, M André11, C Haioun12, G A Salles13, P Gaulard2, H Tilly5, J P Jais14, T J Molina3,15. 1. Pathology, CHU Dijon, Dijon. 2. Pathology, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil, Créteil and IMRB, INSERM U955 Unité, Créteil. 3. Pathology, AP-HP, Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris. 4. Hematology, AP-HP, Necker Enfants-Malades, Paris. 5. Hematology and UMR918, Centre Henri Becquerel, Université de Rouen, Rouen. 6. Hemato-Oncology, AP-HP, Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité and EA 7324, Paris Descartes, Sorbonne Paris Cité, Paris. 7. Functional Genomic Platform, Cancer Research Institute, Lille. 8. Hematology, CHU Nancy, Nancy. 9. Pathology, AP-HP, Saint-Antoine, Paris. 10. Pathology, CHU Bordeaux, Inserm U1053, Bordeaux, France. 11. Hematology, Université Catholique de Louvain, CHU UCL Namur, Yvoir, Belgium. 12. Lymphoid Malignancies Unit, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil, Créteil. 13. Haematology, Hospices Civils de Lyon, Université Claude Bernard, Pierre Bénite. 14. Biostatistics, AP-HP, Necker Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, Paris. 15. EA7324, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Abstract
BACKGROUND: Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. PATIENTS AND METHODS: We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. RESULTS: The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). CONCLUSIONS: Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. CLINICAL TRIAL NUMBER: NCT00144755.
BACKGROUND: Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. PATIENTS AND METHODS: We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. RESULTS: The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). CONCLUSIONS: Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. CLINICAL TRIAL NUMBER: NCT00144755.
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Authors: Marek Trnĕný; Gregor Verhoef; Martin Js Dyer; Dina Ben Yehuda; Caterina Patti; Miguel Canales; Andrés Lopez; Farrukh T Awan; Paul G Montgomery; Andrea Janikova; Anna M Barbui; Kazimierz Sulek; Maria J Terol; John Radford; Anna Guidetti; Massimo Di Nicola; Laure Siraudin; Laurence Hatteville; Sandrine Schwab; Corina Oprea; Alessandro M Gianni Journal: Haematologica Date: 2018-05-10 Impact factor: 9.941