Peripheral Blood Lymphocyte/Monocyte Ratio At 6 Months After Remission As a Predictor Of Relapse After R-CHOP Therapy In Patients With Diffuse Large B-Cell Lymphoma
Authors: Watanabe Reina , Tomita Naoto , Ishiyama Yasufumi , Kishimoto Kumiko , Yamamoto Eri , Ishii Yoshimi , Takahashi Hiroyuki , Miyashita Kazuho , Hattori Yukako , Ito Satomi , Miyazaki Takuya , Takasaki Hirotaka , Kawasaki Rika , Kuwabara Hideyuki , Tanaka Masatsugu , Koharazawa Hideyuki , Taguchi Jun , Fujimaki Katsumichi , Sakai Rika , Ishigatsubo Yoshiaki 
Published: October 2019

Abstract

Background
The prognosis of diffuse large B-cell lymphoma (DLBCL) has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience relapses after achieving first complete remission (CR), leading to poor survival. Although a specific predictor of relapse of non-Hodgkin’s lymphoma has not been identified thus far, recently, the peripheral blood lymphocyte/monocyte ratio (LMR) at diagnosis, which reflects the host’s immune status, was reported to predict clinical outcomes in DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, the significance of LMR as a predictor of relapse in DLBCL patients in remission is not clear. The aim of this study was to assess whether LMR at 6 months after remission is a predictor of relapse after R-CHOP therapy in DLBCL patients.

Methods
From 2003 to 2009, 357 consecutive DLBCL patients were diagnosed, treated with R-CHOP, and followed up at 1 of the 7 participating hospitals in Japan. Of these, 315 DLBCL patients achieved CR after 6–8 cycles of R-CHOP therapy. Among the 315, those who were in remission for more than 6 months (n = 280) were enrolled in this study. The cumulative incidence of relapse was calculated from 6 months after CR to the first subsequent relapse or last follow-up. The effects of risk factors of relapse were assessed in univariate and multivariate Cox regression analyses. In multivariate analysis, risk factors tested at the time of diagnosis, confirmed remission and 6 months after remission included gender, International Prognostic Index at diagnosis (age > 60 years, elevated lactate dehydrogenase level, poor Eastern Cooperative Oncology Group performance status [ECOG PS], the presence of 2 or more extranodal involvement sites, and advanced clinical stage), and LMR ≤ 3.3.

Results
The study included 161 men and 119 women, with a median age of 64 years at diagnosis (range, 18–80 years). The median LMR at 6 months after remission was 3.7 (range, 0.5–18.0). The median observation period for surviving patients was 63 months. In all, 35 (12.5%) patients had confirmed relapse after achieving first CR, with a median time to relapse of 23 months (range, 6–61 months). The estimated 5-year cumulative incidence rate of relapse for the entire cohort was 14.7%. According to the LMR at 6 months after remission, the 5-year cumulative incidence rate for LMR ≤ 3.3 was 17.0% compared to 12.7% for LMR > 3.3 (P = 0.188). In the univariate analysis, advanced clinical stage at diagnosis (hazard ratio [HR] = 2.61, 95% confidence interval [CI], 1.33–5.13, P = 0.005) and poor ECOG PS at diagnosis (HR = 2.62, 95% CI, 1.19–5.77, P = 0.017) were associated with the occurrence of relapse. Multivariate analysis identified advanced clinical stage at diagnosis (HR = 2.42, 95% CI, 1.11–5.27, P = 0.026) and LMR ≤ 3.3 at 6 months after remission (HR = 2.10, 95% CI, 1.01–4.35, P = 0.047) as the risk factors for relapse.

Conclusions
The LMR at 6 months after remission is an independent predictor of relapse in first CR in DLBCL patients treated with R-CHOP.

Disclosures:
No relevant conflicts of interest to declare.