Survival Benefit of R-ACVBP vs R-CHOP in Diffuse Large B-Cell Lymphoma Attributable to Effect in Patients With Non–Germinal Center B-Cell–Like Tumors
In an analysis of the French phase III LNH 03-2B trial reported in the Journal of Clinical Oncology, Molina et al found that germinal center B-cell–like vs non–germinal center B-cell–like subclassification of diffuse large B-cell lymphoma according to the Hans algorithm was associated with the improved survival observed with dose-intensive rituximab (Rituxan), doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) vs standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP).
Study Details
The study involved data from 229 patients aged 18 to 59 years with low-/intermediate-risk diffuse large B-cell lymphoma in the Groupe d’Etudes des Lymphomes de l’Adulte/Lymphoma Study Association LNH 03-2B trial who had tumors evaluable for germinal center B-cell–like and non–germinal center B-cell–like classification according to the Hans algorithm (using CD10, BCL6, and MUM1 expression with cutoff levels of 30%). Expression of CD10, BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were measured by immunohistochemistry.
Germinal center B-cell–like tumors were present in 46 R-ACVBP patients and 55 R-CHOP patients, and non–germinal center B-cell–like tumors were present in 61 and 67.
No Significant Markers in Total Population
In the entire population, no significant effect on progression-free survival or overall survival was found for any of the individual immunohistochemical markers, the Hans algorithm, or the MYC-/BCL2-positive combination, and there was no difference in progression-free survival (P = .90) or overall survival (P = .68) between germinal center B-cell–like and non–germinal center B-cell–like profiles.
Significant Interaction Between Hans Algorithm and Treatment
Among all biomarkers, only the interaction between the Hans algorithm and treatment group was significant for both progression-free survival (P = .04 on univariate analysis, P = .03 on multivariate analysis adjusting for clinical parameters) and overall survival (P = .01 on both univariate and multivariate analysis). Non–germinal center B-cell–like tumors were associated with poorer progression-free survival (hazard ratio [HR] = 3.21, P = .01) and overall survival (HR = 6.09, P = .02) among patients treated with R-CHOP vs those treated with R-ACVBP. No significant differences were observed between treatments among patients with germinal center B-cell–like tumors.
The investigators concluded: “The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to improved survival among patients with [non–germinal center B-cell–like diffuse large B-cell lymphoma]. Therefore, the Hans algorithm could be considered a theragnostic biomarker for selecting young patients with [diffuse large B-cell lymphoma] who can benefit from an intensified R-ACVBP immunochemotherapy regimen.”
Thierry Jo Molina, MD, PhD, of Université Paris Descartes, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the Lymphoma Study Association/Groupe d’Etudes des Lymphomes de l’Adulte, Institut National du Cancer, and Amgen.
For full disclosures of the study authors, visit jco.ascopubs.org.
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