Prognostic Impact Of Gender In Diffuse Large B Cell Lymphoma Patients Treated With R-CHOP Therapy
Authors: Takahashi Hiroyuki , Tomita Naoto , Kawasaki Rika , Hashimoto Chizuko , Yamazaki Etsuko , Taguchi Jun , Sakai Rika , Fujisawa Shin , Ogawa Koji , Ishigatsubo Yoshiaki 
Published: October 2019

Abstract

Background
Since the introduction of rituximab, an anti-CD20 monoclonal antibody, the prognosis of patients with CD20-positive non-Hodgkin lymphoma has significantly improved. Recent reports have shown a gender-associated difference in rituximab clearance and clinical response, suggesting that rituximab may be more effective in female patients. However, the prognostic impact of gender with regard to rituximab clearance in diffuse large B-cell lymphoma (DLBCL) patients has not been elucidated thus far.

Methods
We retrospectively analyzed data from 368 consecutive DLBCL patients, uniformly treated with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21) therapy in 7 institutions in Japan, between 2001 and 2009. Patients with a dose reduction greater than 20%, mainly elderly patients with low performance status, were excluded from this study. The median age of the cohort was 64 years (range, 18–80 years), and 209 (57%) of the patients were male.

Results
With respect to the International Prognostic Index (IPI) factors, a significantly higher proportion of female patients had elevated serum lactate dehydrogenase (sLDH) levels than male patients (56% vs. 44%, P = 0.02). A difference was also observed in the frequency of bone marrow (BM) involvement, which was primarily observed in male patients (8% in women vs. 18% in men, P = 0.006). No difference was observed between sexes in other baseline factors (additional IPI factors, bulky mass over 10 cm, B symptoms). Complete remission rate for R-CHOP-21 was 86% in female patients and 91% in male patients (P = 0.1). After a median follow-up of 36 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 74.9% and 84.5%, respectively. The IPI on diagnosis was low for 158 (42.9%) patients, low-intermediate for 93 (25.3%) patients, high-intermediate for 57 (15.5%) patients, and high for 60 (16.3%) patients, with significant differences in survival among the 4 groups (3-year OS: 93.8%, 85.2, 82.6%, and 60.2%, respectively, P < 0.001). Univariate analysis revealed that advanced clinical stage, poor performance status (PS 2-4), elevated sLDH, more than 1 extranodal involvement, BM involvement, bulky mass over 10 cm, and B symptoms had prognostic impact for both PFS and OS. However, there was no significant difference in the survival rate between female and male patients (3-year PFS; 72.7% vs. 78.0%, P = 0.4; 3-year OS; 82.7% vs. 76.5%, P = 0.4). Moreover, gender did not have an impact on prognosis among younger (<60 years)/elderly (>60 years), normal/elevated sLDH, and positive/negative BM involvement patients’ cohort. Multivariate analysis revealed that clinical stage (P = 0.001 for PFS, 0.02 for OS), sLDH (P = 0.03 for PFS), PS (P= 0.005 for OS), and bulky mass (0.02, 0.04) had a prognostic impact, whereas gender was not identified as a prognostic factor.

Conclusion
Although a difference in the rate of rituximab clearance has been previously reported, gender was not found to be a prognostic factor among DLBCL patients receiving uniform R-CHOP therapy in this study.

Disclosures:
No relevant conflicts of interest to declare.