Efficacy Of Rituximab To Chemotherapy In The Treatment Of EBV-Positive Diffuse Large B-Cell Lymphoma

EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a provisional entity included in the 2008 WHO Classification. EBV+ DLBCL of the elderly is characterized by an aggressive clinical course and a poor outcome. Furthermore, it is unclear if patients with EBV+ DLBCL of the elderly benefit from the addition of rituximab to chemotherapy. The goal of this retrospective study is to evaluate the clinical relevance of rituximab in this entity in a cohort of Peruvian patients.

Between January 2002 and December 2012, all patients meeting criteria for EBV+ DLBCL were included in the analysis. Patients with evidence of immunosuppression were excluded. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or PAX-5 expression by immunohistochemistry. Clinical data were reviewed retrospectively and patients’ biopsies were evaluated for the immunohistochemical expression of BCL6, CD10, and MUM-1/IRF4. Overall survival (OS) was defined as the time between diagnosis and death or last follow-up. The Kaplan-Meiermethod was used to estimate OS curves, which were then comparedusing the log-rank test. P-values <0.05 were considered statistically significant.

A total of 42 EBV+ DLBCL patients are included in this study. The median age at diagnosis was 73 years (range 25-95 years). The male-to-female ratio was 2.2:1.  B symptoms were observed in 59%, a performance status ECOG >1 in 60%, advanced stage (III/IV) in 58%, and elevated LDH levels in 44% of the patients. Based on the Hans classification, 81% had a non-germinal center profile. The median Ki67 expression was 80% (range 50-90%). The Oyama score distribution, which uses age >70 and presence of B symptoms, was 0 factors 14%, 1 factor 45% and 2 factors in 40% of the patients. Based on the International Prognostic Index (IPI) score, 0-2 factors were seen in 39% and 3-5 in 61% of the patients. Chemotherapy was not administered in 9 patients due to poor performance status. R-chemotherapy was administered in 17 patients (52%) and chemotherapy without rituximab in 16 patients (48%). The overall response rate (ORR) was 52%, with complete response (CR) in 42%, partial response (PR) in 9% and no response (NR) in 48%. The response rates in patients who received chemotherapy without rituximab were: CR 37.5%, PR 0%, and NR 62.5%. Response rates in patients who received R-chemotherapy were: CR 47%, PR 17%, and NR 35%. The odds ratio for a CR was 2.48 (95% CI 0.49-13.2; p=0.21) for patients receiving R-chemotherapy when compared with patients who received chemotherapy alone. The median OS for treated patients was 8 months with a 3-year OS of 40%. For patients receiving R-chemotherapy, the median OS was 20 months with a 3-year OS of 47% and for patients receiving chemotherapy without rituximab, the median OS was 5 months with a 3-year OS of 37.5% (log-rank p=0.12). The median OS in patients 60 and older was significantly superior with R-chemotherapy in comparison with chemotherapy alone (20 vs. 1.5 months, log-rank p=0.02)

Based on the results of our retrospective study, the addition of rituximab to chemotherapy show a statistical trend towards improved survival rates versus chemotherapy alone in our cohort of patients with EBV+ DLBCL. In a subset analysis, the addition of rituximab to chemotherapy showed a survival benefit in our cohort of EBV+ DLBCL patients 60 years of age and older .

No relevant conflicts of interest to declare.