Thierry Jo Molina1, Danielle Canioni2, Christiane Copie-Bergman2, Christian Recher2, Josette Brière2, Corinne Haioun2, Françoise Berger2, Christophe Fermé2, Marie-Christine Copin2, Olivier Casasnovas2, Catherine Thieblemont2, Tony Petrella2, Karen Leroy2, Gilles Salles2, Bettina Fabiani2, Franck Morschauser2, Nicolas Mounier2, Bertrand Coiffier2, Fabrice Jardin2, Philippe Gaulard2, Jean-Philippe Jais2, Hervé Tilly2. 1. Thierry Jo Molina, Danielle Canioni, and Jean-Philippe Jais, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Enfants-Malades, Université Paris Descartes, EA 7324, Sorbonne Paris Cité; Josette Brière and Catherine Thieblemont, AP-HP, Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité; Catherine Thieblemont, L'Institut National de la Santé et de la Recherche Médicale (INSERM) U728; Bettina Fabiani, AP-HP, Saint-Antoine, Paris; Christiane Copie-Bergman, Corinne Haioun, Karen Leroy, and Philippe Gaulard, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil; Christiane Copie-Bergman, Karen Leroy, and Philippe Gaulard, INSERM Unité U955 Équipe 9, Créteil; Christian Recher, Centre Hospitalier Universitaire (CHU) Purpan, Université Toulouse III Paul Sabatier, Toulouse; Françoise Berger, Gilles Salles, and Bertrand Coiffier, Hospices Civils de Lyon, Université Claude Bernard, Pierre-Bénite; Christophe Fermé, Institut Gustave Roussy, Villejuif; Marie-Christine Copin and Franck Morschauser, CHU Lille, Lille; Olivier Casasnovas and Tony Petrella, CHU Dijon, Dijon; Nicolas Mounier, CHU Nice, Nice; and Fabrice Jardin and Hervé Tilly, Centre Henri Becquerel, Université de Rouen, Rouen, France. thierry.molina@nck.aphp.fr. 2. Thierry Jo Molina, Danielle Canioni, and Jean-Philippe Jais, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Enfants-Malades, Université Paris Descartes, EA 7324, Sorbonne Paris Cité; Josette Brière and Catherine Thieblemont, AP-HP, Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité; Catherine Thieblemont, L'Institut National de la Santé et de la Recherche Médicale (INSERM) U728; Bettina Fabiani, AP-HP, Saint-Antoine, Paris; Christiane Copie-Bergman, Corinne Haioun, Karen Leroy, and Philippe Gaulard, AP-HP, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est Créteil; Christiane Copie-Bergman, Karen Leroy, and Philippe Gaulard, INSERM Unité U955 Équipe 9, Créteil; Christian Recher, Centre Hospitalier Universitaire (CHU) Purpan, Université Toulouse III Paul Sabatier, Toulouse; Françoise Berger, Gilles Salles, and Bertrand Coiffier, Hospices Civils de Lyon, Université Claude Bernard, Pierre-Bénite; Christophe Fermé, Institut Gustave Roussy, Villejuif; Marie-Christine Copin and Franck Morschauser, CHU Lille, Lille; Olivier Casasnovas and Tony Petrella, CHU Dijon, Dijon; Nicolas Mounier, CHU Nice, Nice; and Fabrice Jardin and Hervé Tilly, Centre Henri Becquerel, Université de Rouen, Rouen, France.
Abstract
PURPOSE: To determine whether any tumor biomarkers could account for the survival advantage observed in the LNH 03-2B trial among patients with diffuse large B-cell lymphoma (DLBCL) and low-intermediate risk according to the International Prognostic Index when treated with dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) compared with standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). PATIENTS AND METHODS: Using immunohistochemistry, expression of CD10, BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were examined. The interaction effects between each biomarker and treatment arm on survival were studied in a restricted model and a full model incorporating clinical parameters. RESULTS: Among the 379 patients analyzed in the trial, 229 tumors were evaluable for germinal center B-cell-like (GCB)/non-GCB subclassification according to the Hans algorithm. Among all the biomarkers, only the interaction between the Hans algorithm and the treatment arm was significant for progression-free survival (PFS) and overall survival (OS) in univariable (PFS, P = .04; OS, P = .01) and multivariable (PFS, P = .03; OS, P = .01) analyses. Non-GCB tumors predicted worse PFS (hazard ratio [HR], 3.21; 95% CI, 1.29 to 8.00; P = .01) and OS (HR, 6.09; 95% CI, 1.37 to 27.03; P = .02) among patients treated with R-CHOP compared with patients who received R-ACVBP, whereas there were no significant survival differences between these regimens among patients with GCB tumors. CONCLUSION: The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to improved survival among patients with non-GCB DLBCL. Therefore, the Hans algorithm could be considered a theragnostic biomarker for selecting young patients with DLBCL who can benefit from an intensified R-ACVBP immunochemotherapy regimen.
RCT Entities:
PURPOSE: To determine whether any tumor biomarkers could account for the survival advantage observed in the LNH 03-2B trial among patients with diffuse large B-cell lymphoma (DLBCL) and low-intermediate risk according to the International Prognostic Index when treated with dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) compared with standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). PATIENTS AND METHODS: Using immunohistochemistry, expression of CD10, BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were examined. The interaction effects between each biomarker and treatment arm on survival were studied in a restricted model and a full model incorporating clinical parameters. RESULTS: Among the 379 patients analyzed in the trial, 229 tumors were evaluable for germinal center B-cell-like (GCB)/non-GCB subclassification according to the Hans algorithm. Among all the biomarkers, only the interaction between the Hans algorithm and the treatment arm was significant for progression-free survival (PFS) and overall survival (OS) in univariable (PFS, P = .04; OS, P = .01) and multivariable (PFS, P = .03; OS, P = .01) analyses. Non-GCB tumors predicted worse PFS (hazard ratio [HR], 3.21; 95% CI, 1.29 to 8.00; P = .01) and OS (HR, 6.09; 95% CI, 1.37 to 27.03; P = .02) among patients treated with R-CHOP compared with patients who received R-ACVBP, whereas there were no significant survival differences between these regimens among patients with GCB tumors. CONCLUSION: The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to improved survival among patients with non-GCB DLBCL. Therefore, the Hans algorithm could be considered a theragnostic biomarker for selecting young patients with DLBCL who can benefit from an intensified R-ACVBP immunochemotherapy regimen.
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