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

• Published in: European journal of haematology 2020-04, Vol.104 (4), p.336-343
• Main Authors: Xu, Jie, Liu, Jing‐Lan, Medeiros, L. Jeffrey, Huang, Wenting, Khoury, Joseph D, McDonnell, Timothy J., Tang, Guilin, Schlette, Ellen, Yin, C. Cameron, Bueso‐Ramos, Carlos E., Lin, Pei, Li, Shaoying
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-cell lymphoma; cell‐of‐origin classification; Classification; Cyclophosphamide - therapeutic use; diffuse large B‐cell lymphoma; double expresser; Doxorubicin - therapeutic use; Female; Genes, bcl-2; Genes, myc; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical prognosis; Middle Aged; Multivariate analysis; Myc protein; MYC rearrangement; Prednisone - therapeutic use; Prognosis; Retrospective Studies; Rituximab - therapeutic use; Survival Analysis; Tumors; Vincristine - therapeutic use; Young Adult
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.13384

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.