Impact of Rituximab and Methotrexate on the Survival of the Patients with Sinonasal Tract Diffuse Large B-Cell Lymphoma
Authors: Vähämurto Pauli , Mannisto Susanna , Pollari Marjukka , Karjalainen-Lindsberg Marja-Liisa , Mäkitie Antti A. , Leppä Sirpa 
Published: October 2019

Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) of the sinonasal track (SNT) is a rare presentation of the aggressive lymphoid malignancy with the incidence of 0.06-0.17 per 100 000 in the Western population. SNT involvement is associated with increased risk of central nervous system (CNS) progression, and thus eligible patients are often treated with chemoimmunotherapy in combination with CNS prophylaxis with intrathecally (it) or intravenously (iv) administered methotrexate (MTX). However, the data demonstrating that the addition of CD20 antibody rituximab and/or CNS penetrating MTX improves the outcome of the patients with SNT-DLBCL are lacking.
Materials and Methods: The aim of the study was to characterize the clinical findings of the patients with SNT-DLBCL treated at two University Hospital districts in Finland (Helsinki and Tampere University Hospitals). The hospital records of 59 patients were retrospectively reviewed on parameters for patient demographics, tumor characteristics, treatment and outcome.
Results: Forty-five patients were treated with curative intent with CHOP-like chemotherapy, 24 (53%) of them with chemoimmunotherapy containing rituximab (R+) and 21 (47%) before the rituximab era (R-). Among the patients treated with curative intent, iv MTX was given to 24 patients (53%; M+ group), whereas the remaining 21 patients (47%) did not receive MTX (M- group). The median age was 65 years for the whole cohort, and 64 years for the patients treated with curative intent. The patients treated with curative intent had better performance status in comparison to all patients. Otherwise, the patient characteristics were similar. Follow-up data was collected to 60 months. Median follow-up time for the entire cohort was 47 months.
No differences were observed in the patient characteristics between the R+ and R- groups. The patients in the M+ group were younger than the patients in the M- group (67% vs 24% were <60 years, p=0.007). Otherwise, no significant differences in the patient characteristics were found between the two groups. MTX was used equally often during the pre-R and R eras.
The patients in the R+ group had lower risk of progression (RR 0.384, 95% CI 0.145-1.018, p=0.054) and death (RR 0.235, 95% CI 0.066-0.836, p=0.025) in comparison to the patients in the R- group. According to Kaplan-Meier analyses, the patients in the R+ group had better survival rates than the patients in the R- group (5-y progression free survival (PFS) 66% vs 38%, p=0.046; 5-y overall survival (OS) 80% vs 43%, p=0.015).
Addition of MTX to chemotherapy also reduced the risk of progression (RR 0.384, 95% CI 0.151-0.977, p=0.044) and death (RR 0.253, 95% CI 0.080-0.795, p=0.019). According to Kaplan-Meier analyses, the patients in the M+ group had better survival rates than the patients in the M- group (5-y PFS, 67% vs 31%, p=0.036; 5-y OS 82% vs 35%, p=0.011). Only one patient in the cohort experienced CNS progression.
Conclusions: SNT-DLBCL patients treated with curative intent with R containing regimen have superior survival in comparison to the patients treated in the pre-R era. Likewise, intravenously administered CNS penetrating MTX improves survival. In this cohort, only one patient experienced CNS progression, and thus the impact of different treatments on the risk of CNS progression could not be evaluated.

Disclosures
Mannisto: SOBI: Honoraria; Pfizer: Honoraria; Gilead: Other: Travel expenses; Celgene: Other: Travel expenses; Novartis: Other: Travel expenses; Amgen: Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Roche: Honoraria, Other: Travel expenses. Leppä:Amgen: Research Funding; Takeda: Honoraria, Other: Travel expenses; Bayer: Honoraria, Research Funding; Mundipharma: Research Funding; Roche: Honoraria, Other: Travel Expenses, Research Funding; Janssen: Research Funding; CTI Life Sciences: Honoraria.