BCL2 Predicts Survival in Germinal Center B-cell-like Diffuse Large B-Cell Lymphoma Treated with CHOP-like therapy and Rituximab
Menée sur une cohorte de 221 cas de lymphome diffus à grandes cellules B, cette étude évalue l'association entre l'expression de BCL2 et la survie lorsque le rituximab est ajouté au protocole de chimiothérapie CHOP
Purpose: We have previously demonstrated the prognostic significance of BCL2 expression in the activated B-cell-like diffuse large B-cells lymphoma (ABC-DLBCL) patients treated with CHOP or CHOP-like therapy. However, after the inclusion of rituximab in the CHOP regimen, several conflicting observations regarding the prognostic value of BCL2 expression have been reported. Patient/Methods: We evaluated the R-CHOP cohort of 221 DLBCL cases with gene expression profiling data. BCL2 protein (n=169), mRNA (n=221) expression and t(14;18) (n=144) were correlated with clinical outcome. The CHOP-cohort (n=181) was used for comparative analysis. Results: BCL2 protein expression has significant impact on overall-survival (OS) and event-free-survival (EFS) in DLBCL (OS p=0.009, EFS p=0.001) and GCB-DLBCL (OS p=0.03, EFS p=0.002), but not in ABC-DLBCL in the R-CHOP cohort. These survival differences were also observed in multivariate analysis. At the mRNA level, this correlation was observed in EFS in DLBCL (p=0.006), but only a trend was observed in GCB-DLBCL (p=0.09). The t(14;18) was detected in 35% of GCB-DLBCL but was not associated with significant differences in survival. Gene-enrichment analysis identified significant enrichment of the DLBCL "stroma-1" signatures and HIF1- signature in BCL2(-)GCB-DLBCL, while TFH cell signatures was enriched in BCL2(+)GCB-DLBCL. Conclusion: The prognostic significance of BCL2 has changed after inclusion of rituximab in the treatment protocol, and is observed in the GCB-DLBCL rather than the ABC-DLBCL. Although rituximab has benefitted patients in both DLBCL subgroups, the BCL2 (+)GCB-DLBCL appears to receive less benefit from this treatment and may require other novel therapeutic intervention.
Clinical Cancer Research , résumé, 2011