Clinical Characteristics and Treatment Outcomes in Patients Diagnosed with Primary Mediastinal Large B-Cell Lymphoma at Princess Margaret Cancer Centre from 1994-2012
Authors: Dyszkiewicz-Korpanty Anna M. , Maganti Manjula , Hodgson David C. , Kuruvilla John G. , Kukreti Vishal , Tiedemann Rodger E. , Sun Alexander , Tsang Richard , Gospodarowicz Mary , Pintilie Melania , Porwit Anna , Crump Michael 
Published: October 2019

Abstract
Introduction: Primary mediastinal B-cell lymphoma (PMBCL) is a rare clinical entity representing less than 2-4% of Non-Hodgkin lymphomas. PMBCL typically occurs in young adults, more often in females, with early stage disease usually limited to the antero-superior mediastinum. PMBCL tends to have a more locally aggressive clinical course with a substantial percentage of patients with primary refractory disease or early relapse. Patients with primary refractory or relapsed disease have a lower probability response to second-line therapy and proceeding to autologous stem cell transplant (ASCT). The optimum chemotherapy regimen and role of radiation are currently the subject of debate; for this reason we evaluated our experience using a uniform treatment policy of combined modality therapy (CMT), including factors that influence patient outcomes.
Methods: We analysed 88 patients (median age 35, range 15-64) diagnosed with PMBCL, treated at Princess Margaret Cancer Centre from 1994-2012. Data on stage, clinical prognostic factors, pathologic characteristics (including presence of sclerosis) treatment and outcome were retrieved from a prospective lymphoma database and pathology reports.
Statistical analysis was performed to assess the overall survival (OS) and progression free survival (PFS) at 5 years; PFS events were progressive disease (PD), relapse or death from any cause. Patient characteristics are shown in Table 1
Results: All patients received treatment with curative intent. In the majority of patients first-line chemotherapy was cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP, 47 patients) or CHOP + rituximab (R-CHOP, 38 patients) (average number of cycles = 6); standard involved field consolidative radiation was given to 68/83 patients (82%), with a median dose of 35 Gy, usually in 20 fractions. Following the first line treatment, 38 patients achieved CR (complete response), 33 patients had PR (partial response), PD occurred in 18 patients, 10 patients with initial response relapsed. 28/88 patients with PD or relapse received second line chemotherapy (cisplatin-based or Mini-BEAM) and 6/28 went on to ASCT. Twenty one of 88 (24 %) patients died from progressive lymphoma, 2/88 died of other causes. Overall survival (OS) at five years was 72.4%, and five year PFS in was 67.7%.
We observed significantly inferior five year-OS and PFS in men by univariate analysis (p=0.019; OS= 51.9% vs 80.2% in women and p=0.022; PFS= 47.6 % vs 75.2% in women, respectively); The presence of sclerosis on tumor biopsy also resulted in inferior OS and PFS (OS= 60.4% vs 89.3 %, p=0.0045; PFS= 56.1% vs 81.7%, p=0.013, respectively);PFS and OS in patients treated with R-CHOP was superior to patients who received chemotherapy without Rituximab( PFS of 84.2% vs 55.8%, p= 0.0099 and OS of 89.2% vs 61.9%, p= 0.012).
In multivariate analysis, male gender and tumor pathology (PMBCL with sclerosis) were predictive of inferior OS (p=0.018 and p= 0.022, respectively) and also, inferior PFS (p= 0.0499 and p= 0.024, respectively); age at diagnosis, stage and bulk did not have independent impact on OS or PFS.
Conclusions: Current therapy with R-CHOP and radiation result in excellent PFS and OS. The reasons for adverse outcomes in males in our cohort and pathological correlates of extensive sclerosis are being explored.
Table 1. Patient characteristics at presentation (n=88) Variable N (%) Females 62(70.4) Stage I 39(44.3) Stage II 42(47.7) Stage III-IV 8(9.1) B symptoms 27(30.7) Elevated LDH 44(50) Bulk > 10 cm 60 (68.2) Extranodal disease 37 (42)

Disclosures
Kukreti: Celgene: Honoraria. Porwit:Beckman-Coulter: Speakers Bureau.