The Presence of M Protein Is Strongly Associated with Very Poor Prognosis in Patients with Extranodal Diffuse Large B-Cell Lymphoma
Authors: Nitta Hideaki , Terui Yasuhito , Yokoyama Masahiro , Mishima Yuko , Nishimura Noriko , Ueda Kyoko , Gunji Tadahiro , Kusano Yoshiharu , Inoue Norihito , Takahashi Anna , Tsuyama Naoko , Takeuchi Kengo , Hatake Kiyohiko 
Published: October 2019

Abstract
Introduction
Several studies concerning extranodal diffuse large B-cell lymphoma (DLBCL) have been reported sporadically. However, no new, valuable prognostic factors have been reported since several risk factors, such as a high international prognostic index (IPI) score, elevated lactate dehydrogenase (LDH) level, poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), advanced stage, and extranodal sites ≥2, were identified.
Methods
To identify new and valuable prognostic factors, we reviewed the medical records of patients with nodal and extranodal DLBCL who were newly diagnosed at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from February 2005 to September 2014, and retrospectively analyzed the data of a total of 463 consecutive DLBCL patients. The cases were nodal DLBCL in 237 patients and extranodal DLBCL in 226 patients. We investigated the relationships between overall survival (OS), progression-free survival (PFS), and age, gender, LDH level, beta-2 microglobulin level (b2MG), performance status (PS), stage, extranodal sites ≥2, Ki-67 index, and M protein in serum protein fraction electrophoresis at diagnosis. Univariate and multivariate analyses of estimated risk factors for OS and PFS in extranodal DLBCL patients were performed using the log-rank test and Cox proportional hazard regression analysis.
Results
In patients with extranodal DLBCL, the median age was 67 years (range, 20-89 years). The median follow-up was 41 months (range, 1-115 months). A serum electrophoresis study detected M protein in 7 patients (3.1%). To adjust the impact of age, gender, LDH level, b2MG, PS, stage, extranodal sites ≥2, Ki-67 index, and the presence of M protein in serum protein fraction electrophoresis at diagnosis for other significant factors for OS, we identified the following risk factors in extranodal DLBCL by univariate analysis: elevated LDH level, elevated b2MG level, stage ≥3, extranodal sites ≥2, and the presence of M protein. Then, we performed multivariate analyses by using all of these factors in the Cox proportional hazard model. M protein (HR 6.78, 95% CI 2.19-20.96, P<0.001) and extranodal sites ≥2 (HR 3.71, 95% CI 1.77-7.80, P<0.001) were identified as independent significant prognostic factors for OS in extranodal DLBCL. Furthermore, we also identified M protein (HR 3.81, 95% CI 1.25-11.60, P=0.019) and extranodal sites ≥2 (HR 2.98, 95% CI 1.45-6.14, P=0.003) as independent significant prognostic factors for PFS by multivariate analysis. Four out of seven patients with M protein died due to lymphoma progression. Median overall survival in patients with extranodal DLBCL with M protein was 12 months (range, 2-114 months) compared with 44 months without M protein (range, 1-115 months, P=0.0038). On the other hand, in patients with nodal DLBCL, M protein (n=10) was not significantly associated with poor OS and PFS.
Conclusions
These results suggest that the presence of M protein in serum protein fraction electrophoresis is significantly associated with very poor OS and PFS in patients with extranodal DLBCL, but not nodal DLBCL. Extranodal DLBCL with M protein is a rare and very poor prognostic subset of DLBCL.
Figure 1. Figure 1.

Disclosures
Yokoyama: Chugai Pharmaceutical CO., LTD.: Consultancy. Mishima:Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.