MYC rearrangement and MYC/BCL2 double expression but not cell-of-origin predict prognosis in R-CHOP treated diffuse large B-cell lymphoma

Objective: Diffuse large B-cell lymphoma (DLBCL) can be classified as germinal center B cell-like (GCB) or activated B cell-like (ABC)/non-GCB based on cell-of-origin (COO) classification. This study evaluated the prognostic significance of COO classification in 250 patients diagnosed with de novo DLBCL who received R-CHOP therapy. We also assessed whether the genomic status of MYC, BCL2, or MYC/BCL2 double expression (DE) could provide additional prognostic information for DLBCL patients. Methods: The clinicopathologic features and outcome of patients with GCB DLBCL were compared to patients with non-GCB DLBCL using Fisher's exact test. The prognostic significance of COO, MYC-R, and MYC/BCL2 DE were studied using multivariate Cox proportional hazard analysis. Results: There were 162 men and 88 women with a median age of 62 years (range, 18-86). Forty-five of 250 (18%) cases harbored MYC rearrangement (R). The frequency of MYC-R was much higher in GCB than in non-GCB tumors (40/165, 24% vs 5/85, 6%) (P = .0001). MYC/BCL2 DE was observed in 53 of 125 (42%) cases. COO classification failed to predict overall survival (OS) in DLBCL patients, either those patients with MYC-R were included (P = .10) or not (P = .27). In contrast, MYC-R and MYC/BCL2 DE significantly correlated with inferior OS (P = .0001 and P = .001, respectively). In multivariate analysis, MYC-R and MYC/BCL2 DE were still independent prognostic factors in DLBCL patients. Conclusions: MYC-R and MYC/BCL2 DE are independent prognostic factors for DLBCL patients treated with R-CHOP. In this cohort, COO classification failed to stratify patient outcome.