Lugano 2013: BCL2 Overexpression and Non–Germinal Center B-cell–like Subtype Predict Poorer Survival in Diffuse Large B-cell Lymphoma
In studies to identify prognostic factors in diffuse large B-cell lymphomas, Thierry J. Molina, MD, PhD, of Paris Descartes University, and colleagues assessed expression of MYC, BCL2, MYC/BCL2, IgM, and germinal center B-cell–like and non–germinal center B-cell–like subtypes in a large series of patients with de novo disease treated with rituximab (Rituxan) and anthracycline-based chemotherapy. As reported at the 12th International Conference on Malignant Lymphoma, Lugano, Switzerland, on June 19 to 22, multivariate analysis showed that BCL2 overexpression and the non–germinal center B-cell–like subtype were significantly associated with poorer progression-free survival and overall survival (Abstract 178).
Study Details
The study involved 670 patients with de novo CD20-positive diffuse large B-cell lymphoma enrolled in six GELA (Groupe d'Etudes des Lymphomes de l'Adulte) LNH-03 trials and stratified according to age and age-adjusted international prognostic index (IPI). Of these, 237 had received intensive R-ACVBP (dose-intensive rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) and 433 had received R-CHOP/R-mini-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). Tumor samples were analyzed by immunohistochemistry using CD10, BCL6, MUM1, MYC (40% threshold), BCL2 (70% threshold), and IgM antibodies on tissue microarrays.
Overall, 304 patients (45.4%) were classified as germinal center B-cell–like subtype and 366 (54.6%) as non–germinal center B-cell–like subtype according to the Hans algorithm. Tumors were positive for IgM in 52.4% of cases, 29.5% of cases were MYC-positive, 55.3% were BCL2-positive, and 21% were positive for BCL2/MYC coexpression.
Predictors of Worse Survival
Progression-free survival and overall survival were significantly worse among patients with high IPI score (P < .0001 for both progression-free and overall survival), non–germinal center B-cell–like subtype (P < .0001 for both), and IgM-positive (P < .0001 for progression-free survival, P = .02 for overall survival), MYC-positive (P < .001, P < .01), BCL2-positive (P < .001 for both), and MYC/BCL2-positive (P = .003, P = .005) tumors.
On multivariate analysis, in addition to IPI score, only BCL2 overexpression and non–germinal center B-cell–like subtype predicted significantly worse progression-free survival (P = .0002 and P = .002, respectively) and significantly worse overall survival (P = .03 and P = .002, respectively). The prognostic values of BCL2 (P = .002 for progression-free survival and P = .02 for overall survival) and non–germinal B-cell–like subtype (P = .002 for both progression-free survival and overall survival) were confirmed when analysis was limited to patients treated with R-CHOP.
The investigators concluded, “Our study confirmed the relevance of immunohistochemistry to identify significant prognostic biomarkers for clinical use. Above all, we fully validated the strong and independent prognostic value of the Hans algorithm, daily used by the pathologists to subtype diffuse large B-cell lymphoma, as well as BCL2 overexpression.”
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