Prognostic Impact of Gender in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Therapy
Authors: Takahashi Hiroyuki , Tomita Naoto , Ishiyama Yasufumi , Koyama Satoshi , Miyashita Kazuho , Nakajima Yuki , Hattori Yukako , Motohashi Kenji , Takasaki Hirotaka , Kawasaki Rika , Hagihara Maki , Hashimoto Chizuko , Takemura Sachiya , Fujimaki Katsumichi , Taguchi Jun , Sakai Rika , Fujita Hiroyuki , Fujisawa Shin , Harano Hiroshi , 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 576 consecutive DLBCL patients, uniformly treated with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21) therapy in 9 institutions in Japan, between 2001 and 2012. 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 63 years (range, 18–89 years), and 331 (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 (57% vs. 48%, P = 0.03). A difference was also observed in the frequency of bone marrow (BM) involvement, which was primarily observed in male patients (8% in female vs. 15% in male, P= 0.006).No difference was observed between sexes in other baseline factors (other IPI factors, bulky mass over 10 cm, B symptoms). Complete remission rate for R-CHOP-21 was 86% in female patients and 85% in male patients (P = NS). After a median follow-up of 48 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 73.7% and 84.3%, respectively. The IPI on diagnosis was low for 238 (41.3%) patients, low-intermediate for 152 (26.4%) patients, high-intermediate for 94 (16.3%) patients, and high for 92 16.0%) patients, with significant differences in survival among the 4 groups (3-year OS: 93.2%, 85.1%, 81.1%, and 63.6%, 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 (all P <0.001). However, there was no significant difference in the survival rate between female and male patients (3-year PFS; 73.9% vs. 73.5%, P = 0.58; 3-year OS; 84.9% vs. 84.0%, P = 0.47). 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 = 0.002 for PFS, 0.009 for OS), bulky mass (0.009, 0.03), B symptom (0.05, 0.02), and sLDH (P = 0.08 for PFS) 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 (Pfreundschuh et. al., Blood 2014), gender was not found to be a prognostic factor among DLBCL patients receiving uniform R-CHOP therapy in this study with Japanese patients’ cohort.

Disclosures
No relevant conflicts of interest to declare.