R-CHOP in the Treatment of EBV-Diffuse Large B-Cell Lymphoma of the Elderly

Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a new entity considered in the most recent WHO classification. It is a very aggressive entity associated with a short survival. The role of rituximab-containing regimens in EBV+ DLBCL of the elderly is currently unknown.

Between January 2002 and December 2010, 22 patients diagnosed with EBV+ DLBCL of the elderly were selected for this study, from which 11 patients received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and 11 patients received rituximab and CHOP (R-CHOP). Both groups received chemotherapy at every 3 weeks cycles. Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the immunohistochemical expression of bcl-6, CD10, CD30 and MUM-1/IRF4. Samples were also analyzed for the presence of EBV-encoded RNA (EBER) using an in situ hybridization (ISH) technique. Chi-square and Mann-Whitney tests were used to compare categorical and continuous variables, respectively. Overall survival (OS) estimates were calculated using the Kaplan-Meier method and compared using the log-rank test. P-values <0.05 were considered statistically significant.

The median age was 73 years (range: 49–85 years) with a male predominance (2.7:1). Eleven patients (50%) had advanced clinical stage (i.e. stage 3 and 4), nine patients (45%) had elevated LDH levels, eleven (50%) had performance status ECOG >1 and 13 (59%) had high or high-intermediate IPI scores. Fourteen out of 17 patients studied (82%) had a non-germinal center DLBCL. When comparing the CHOP and R-CHOP groups, there was no statistical difference in median age (p=0.87), sex distribution (p=0.63), stage distribution (p=0.28), IPI scores (p=0.15), Oyama scores (p=0.23), ECOG performance status (p=0.39), LDH levels (p=0.62), lymphocyte counts (p=0.06), hemoglobin levels (p=0.20), platelet counts (p=0.14), Ki67 expression by malignant cells (p=0.57) and proportion of patients with a non-germinal center profile (p=0.91). Additionally, there was no statistical difference in overall response and complete response rates (p=0.66). When evaluating median OS, patients treated with CHOP and R-CHOP had median OS at 5 and 20 months, respectively (p=0.04).

Based on the results of this retrospective study, patients with EBV+ DLBCL of the elderly had a short OS when treated with CHOP alone; however, R-CHOP seems to confer a survival advantage in patients with EBV+ DLBCL of the elderly, although it seems shorter than in EBV-negative DLBCL patients.

Castillo:GlaxoSmithKline: Research Funding; Millennium Pharmaceuticals: Research Funding.