Clinical Significance of Immunohistochemical Markers of Diffuse Large B-Cell Lymphoma In the Rituximab Era.
Authors: Hayama Miyuki , Okamoto Masataka , Hagiwara Yuki , Tanae Ken , Kohri Mika , Takahashi Naoki , Yoshino Tadashi , Ohshima Koichi , Niitsu Nozomi 
Published: October 2019

Abstract
Abstract 1800
Rituximab combination chemotherapy has significantly improved the treatment outcome of diffuse large B-cell lymphoma (DLBCL). Therefore, the prognostic factors of DLBCL in the rituximab era are different from previously reported prognostic factors. Biological prognostic markers have been analyzed to help understand the biologic basis of treatment outcome. Hans, et al. reported that patients with non-germinal center B-cell like (GCB)-type DLBCL had a significantly poorer prognosis than those with GCB-type DLBCL in the pre-rituximab era. In patients who received rituximab combination chemotherapy, there is a report that did not find a difference in survival ratio between those with GCB DLBCL or non-GCB DLBCL. On the other hand, there was a report that found a difference in survival ratio between patients with GCB DLBCL and those with non-GCB DLBCL.
In the present study, we compared the prognostic factors of DLBCL between patients who received CHOP-like chemotherapy and those who received rituximab combined with CHOP-like therapy. The subjects were 204 DLBCL patients who underwent rituximab + CHOP-like therapy and in whom markers could be analyzed. We evaluated CD5, CD10, BCL2, BCL6, and MUM1 expression by immunohistochemistry. One hundred forty-six DLBCL patients who underwent CHOP-like therapy were assumed as historical controls. The median age was 52 years in both groups. In the R-CHOP-like and CHOP-like groups, patients with stage III or IV disease comprised 75% and 67%, respectively, patients with performance status3a2 comprised 28% and 20%, respectively, and patients with serum LDH >normal comprised 60% and 77%, respectively. There were no significant differences in clinical characteristics between the CHOP-like group and R-CHOP-like group. BCL2 was positive in 85(63%) of the 134 patients who received the R-CHOP-like regimen and in 66 (46%) of the 142 patients who received the CHOP-like regimen. When the 202 patients who received the R-CHOP-like regimen were divided into the GCB group and the non-GCB group, the GCB group consisted of 92 patients (46%) and the non-GCB group consisted of 110 patients. The relationships between immunohistological markers and outcome among the patients with DLBCL who received CHOP-like therapy were studied. CD5, CD10, and BCL6 had no prognostic impact on 5-year overall survival (OS) and progression-free survival (PFS) rates. When the patients were divided into the GCB DLBCL and non-GCB DLBCL groups, the 5-year OS of the GCB group was 78% and that of the non-GCB group was 57% (p<0.05). The 5-year PFS of the GCB group was 73% and that of the non-GCB group was 52% (p<0.05). The 5-year OS rate of the BCL2-positive and -negative groups was 61% and 74%, respectively (p<0.05). The 5-year PFS rate of the BCL2-positive and -negative groups was 55% and 70%, respectively (p<0.05). Thus, among patients who received the CHOP-like regimen, the BCL2-positive group showed significantly poorer prognosis than the BCL2-negative group. Next, the effect of rituximab with chemotherapy was examined. CD5, CD10, BCL2, BCL6, and MUM-1 had no prognostic impact on 5-year OS and PFS rates. When the patients were divided into the GCB DLBCL (n=92) and non-GCB DLBCL (n=110) groups, the 5-year OS of the GCB group was 74% and that of the non-GCB group was 75%, showing no significant difference. The 5-year PFS of the GCB group was 71% and the 5-year PFS of the non-GCB group was 69%, showing no significant difference. In the rituximab era, BCL2, MUM1 and non-GCB were not prognostic factors. As to reports on patients with DLBCL who received rituximab combination chemotherapy, there was a report in which the cases were separated into the GCB-type DLBCL and non-GCB-type DLBCL groups and compared. Fu, et al. reported that the survival of patients with GCB-type DLBCL was still superior to that of patients with non-GCB-type DLBCL in the rituximab era. However, other reports did not find a difference in survival ratio between those with GCB-type DLBCL or non-GCB-type DLBCL.
In conclusion, the finding of improved OS and PFS with the addition of rituximab indicates that new biomarkers should be studied.

Disclosures:
No relevant conflicts of interest to declare.