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CD30 expression in EBV+ DLBCL confers poor prognosis


 

FROM THE ANNUAL ICML

Epstein-Barr virus-positive diffuse large B-cell lymphoma, or EBV+ DLBCL, represents only a small proportion of DLBCLs, and has an activated B-cell type immunophenotype and a unique gene expression profile and genetic signature that distinguish the neoplasm from EBV-negative DLBCL, according to a report from the International DLBCL Rituximab-CHOP Consortium Program Study.

Further, CD30 expression is more common in EBV+ DLBCL than in EBV-negative DLBCL and confers an adverse outcome, Dr. Ken He Young reported at the annual International Conference on Malignant Lymphoma in Lugano, Switzerland.

The findings are based on a study of 451 HIV-negative de novo DLBCL patients who had tissue microarrays from primary biopsy specimens available. All were uniformly treated with rituximab plus chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), said Dr. Young of the department of hematopathology at the University of Texas MD Anderson Cancer Center, Houston (Hematol. Oncol. 2013;31[(Suppl 1]:96-150[abstract 9]).

Of the 451 patients, 27 (6%) had positive EBV-encoded RNA (EBER) test results, defined as reactivity in more than 10% of malignant cells. The median age of the EBV+ and EBV- patients was similar at 61 and 64 years, respectively, as were the presenting clinical characteristics, Dr. Young noted.

However, an activated B-cell type signature occurred in 70% of EBV+ patients, compared with 48% or 49% (based on gene expression profiling and immunohistochemistry using the Visco-Young algorithm, respectively) in the EBV- patients, and CD30 expression occurred in 48% of EBV+ patients, compared with 15% of EBV- patients, he said.

No difference was seen in the expression of BCL2, MYC or both proteins between the EBV+ and EBV- groups, but the EBV+ patients had no detrimental TP53 mutation and only 18% presented rearrangements involving BCL2, C-MYC, or BCL6 genes.

Five-year overall survival appeared inferior in the EBV+ DLBCL patients at 50%, compared with 62% for the EBV- DLBCL patients, even after stratification by age, but the difference between the groups did not reach statistical significance. The same was true for progression-free survival, Dr. Young noted.

Among EBV+ DLBCL patients with CD30 expression, however, the prognosis was dismal, with median overall and progression-free survival of 37% and 35%, respectively, compared with 74% and 56%, respectively, in those with CD30 negative EBV+ DLBCL. These differences were statistically significant, Dr. Young said, adding that gene expression profiling revealed a unique expression signature in EBV+ DLBCL with NF-kB pathway activation.

In a separate report from the International DLBCL Rituximab-CHOP Consortium Program Study published online in May in Blood, Dr. Young and his colleagues explained that EBV+ DLBCL of the elderly, which was initially described 10 years ago, is a provisional entity within the World Health Organization classification system, and is defined as "an EBV-positive monoclonal large B-cell proliferation that occurs in patients greater than 50 years of age and in whom there is no known immunodeficiency or history of lymphoma," (2013;121: 2715-24 [doi:10.1182/blood-2012-10-461848]).

"It is hoped that the improved understanding of these tumors will lead to development of novel therapeutic approaches, enhance the effective clinical trials, and improve the prognosis," the investigators said.

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