Comparison Between R-CHOP Vs R-CHOP Plus Etoposide in Untreated Patients with Primary Mediastinal B-Cell Lymphoma: Preliminary Findings
Authors: Maciel Felipe Vieira Rodrigues , Szor Roberta Shcolnik , Levy Debora , Santucci Rodrigo , Pereira Juliana 
Published: October 2019

Abstract
Background:
Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma originating from the thymus with its own epidemiological, clinical, immunophenotypic and prognostic features and that was included as a distinct clinical entity in the last World Health Organization classification (2008). It is more prevalent in young female, and is characterized by a large mediastinal mass, with frequent infiltration of adjacent structures. Dissemination by distant sites may be identified at diagnosis or during the disease progression. It shows many similar aspects to nodular sclerosis Hodgkin’s Lymphoma in terms of clinical, pathological and immunohistochemical features.
The standard treatment is based on multidrug regimens containing anthracyclines associated with rituximab and consolidation with radiotherapy. A recent study published in the NEJM in 2013, with a single-arm treatment with infusional dose-adjusted DA-EPOCH-R with no radiotherapy in untreated PMBCL, demonstrated 97% of overall survival (OS) and 93% of event-free survival (EFS) with a median of 5 years of follow-up.
Methods:
We analyzed retrospectively 40 patients with PMBCL treated at São Paulo’s Cancer Institute from June 2007 to January 2014. The objectives of the study were to compare the complete response (CR), progression-free survival (PFS) and overall survival (OS) rates between two different treatment strategies. All patients were initially evaluated with blood tests, whole-body computed tomography (CT) or fluorodeoxyglucose-positron-emission tomography (PET-CT) and bone marrow biopsy. Two chemotherapy regimens were used in the patient’s treatment: 6 to 8 cycles of conventional R-CHOP 21 with or without radiation therapy (n = 23) and R-CHOP regimen with addition etoposide (DA-EPOCH-R or R-CHOEP) with or without radiotherapy (n = 17). After 4 cycles of treatment, patients were evaluated for response to determine the total number of cycles (6 or 8).
Results
Among the 40 enrolled patients, 65% were female with median age of 31 years (range 14 to 62 years). The median size of the mediastinal mass was 13cm in the longest axis. Half of the patients (50%) were in advanced stage (III or IV of Ann Arbor staging) and 75% were in good prognosis category of R-IPI ( 1 or 2 risk factors of the International Prognostic Index Score for non Hodgkin lymphoma). 57,5% of patients were treated with R-CHOP and 42,5% had etoposide as part of the their treatment regimen (12,5% DA-EPOCH-R and 30% R-CHOP plus etoposide (100mg/m2 D1-D3). There was no statistically significant difference in CR rate between RCHOP vs RCHOP + etoposide (86.9% vs 86.6%). There were no differences in PFS or OS for the 2 groups (p=0.8202 and 0.9410).
Conclusion
The addition of etoposide to RCHOP regimen appears to increase OS and PFS of patients with untreated PMBCL as previously demonstrated. In our service, where there is difficult in hospitalization for the administration of infusional regimens such as DA-EPOCH-R, it was necessary to adjust for outpatient to R-CHOEP. The comparison between the two groups (RCHOP vs RCHOEP/DA-EPOCH-R) showed no statistically significant difference in CR, OS and PFS. However, the median of follow-up of patients who received etoposide was not sufficient to analyze the data adequately.
Overall Survival
Figure 1. Overal survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.8202) Figure 1. Overal survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.8202)
Progression Free Survival
Figure 2. Progression free survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.9410). Figure 2. Progression free survival betwen R-CHOP and R-CHOEP in PMBCL (p = 0.9410).

Disclosures
No relevant conflicts of interest to declare.