Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B.

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.

• Authors: Thierry Jo Molina, Danielle Canioni, Christiane Copie-Bergman, Christian Recher, Josette Brière, Corinne Haioun, Françoise Berger, Christophe Fermé, Marie-Christine Copin, Olivier Casasnovas, Catherine Thieblemont, Tony Petrella, Karen Leroy, Gilles Salles, Bettina Fabiani, Franck Morschauser, Nicolas Mounier, Bertrand Coiffier, Fabrice Jardin, Philippe Gaulard, Jean-Philippe Jais, Hervé Tilly
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 35 Pg. 3996-4003 (Dec 10 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25385729 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• BCL6 protein, human
• Biomarkers, Tumor
• CCL2 protein, human
• Chemokine CCL2
• DNA-Binding Proteins
• Interferon Regulatory Factors
• MYC protein, human
• Proto-Oncogene Proteins c-bcl-6
• Proto-Oncogene Proteins c-myc
• R-CHOP protocol
• interferon regulatory factor-4
• Bleomycin
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisolone
• Neprilysin
• Vindesine
• Prednisone

Topics

• Adult
• Algorithms
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor
• Bleomycin (therapeutic use)
• Chemokine CCL2 (metabolism)
• Cyclophosphamide (therapeutic use)
• DNA-Binding Proteins (metabolism)
• Disease-Free Survival
• Doxorubicin (therapeutic use)
• Female
• Humans
• Immunohistochemistry
• Immunotherapy (methods)
• Interferon Regulatory Factors (metabolism)
• Kaplan-Meier Estimate
• Lymphoma, Large B-Cell, Diffuse (drug therapy, mortality)
• Male
• Middle Aged
• Neprilysin (metabolism)
• Prednisolone (therapeutic use)
• Prednisone (therapeutic use)
• Proportional Hazards Models
• Proto-Oncogene Proteins c-bcl-6
• Proto-Oncogene Proteins c-myc (metabolism)
• Rituximab
• Treatment Outcome
• Vincristine (therapeutic use)
• Vindesine (therapeutic use)