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

Abstract

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.

Immunophenotypic Landscape and Prognosis of Diffuse Large B-Cell Lymphoma with MYC/BCL2 Double Expression: An Analysis of A Prospectively Immunoprofiled Cohort

“…Hu et al and Green et al demonstrated that DE status was associated with a poor prognosis in both GCB and ABC/non-GCB-DLBCLs [12,13]. In contrast, other studies have reported that, despite the association between DE status and poor prognosis in GCB-DLBCLs, DE status could not predict survival in patients with ABC/non-GCB-DLBCLs [23,25,28]. These discrepancies might be attributed to differences in the methods used for COO classification among studies, characteristics of study populations, and the retrospective or prospective nature of data collection.…”

Consecutive Hypoalbuminemia Predicts Inferior Outcome in Patients With Diffuse Large B-Cell Lymphoma

“…Along with this, the prognostic significance of international prognostic index (IPI) was impaired and could only distinguish the low-risk with the high-risk group instead of the four risk groups as previously described (3)(4)(5). Alternatively, more and more clinical and biological markers were explored to predict the prognosis of DLBCL, including age, extranodal lesions, cell of origin, c-MYC and Bcl-2 co-expression or translocation, and different biochemical indicators (6)(7)(8)(9)(10)(11)(12)(13)(14). As the treatment developed, the prognostic values of these biochemical indicators may also change.…”

Anaplastic lymphoma kinase (ALK)‐negative anaplastic large cell lymphoma with MYC rearrangement

“…MYC is altered in many malignancies including lymphomas and some solid tumours 3 . Although the role of MYC dysregulation has been studied extensively in B‐cell lymphomas, 4–8 studies of MYC aberrations in T‐cell lymphomas are very limited. A few reports suggest that T‐cell lymphomas often have increased MYC copy number, but rarely carry MYC rearrangement ( MYC ‐R) 9‐12 .…”

“…3 In these situations, few data regarding management of the risk of relapse are available. 5,6 Our group proposed an intensive rituximab regimen inspired by the maintenance treatment of B-cell-indolent lymphoid malignancies. 7 We report here our experience with this strategy in iTTP patients who are unresponsive to standard pre-emptive rituximab treatment.…”