What is the role of chemoimmunotherapy in the treatment of primary mediastinal B-cell lymphoma (PMBCL)?

Updated: Sep 14, 2019
  • Author: Sonali M Smith, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Combination anthracycline-based chemotherapy is the mainstay of treatment for primary mediastinal B-cell lymphoma (PMBCL). The standard front-line regimen in the United States is cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisone combined with rituximab (CHOP-R). Rituximab is a chimeric monoclonal anti-CD20 antibody that has transformed how B-cell lymphomas are treated and has become a standard component of treating all B-cell lymphoma histologies that express CD20. 

A few studies, mainly from Europe, have advocated themethotrexate, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), prednisone, and bleomycin (MACOP-B) regimen, combined with rituximab. [24, 25, 26] The standard CHOP-R regimen is now being challenged by a combination program that contains etoposide (dose-adjusted EPOCH) plus rituximab (DA-EPOCH-R), although prospective randomized trials to accurately compare these 2 programs (CHOP-R vs DA-EPOCH-R) have not been completed. [27]  Nevertheless, the National Comprehensive Cancer Network (NCCN) guidelines recommend DA-EPOCH-R as the preferred first-line treatment for PMBCL. [20]

As PMBCL was recognized only recently as being a distinct entity, original studies that have established CHOP-R as a standard therapy in diffuse large B-cell lymphoma (DLBCL) did not include PMBCL patients. Accordingly, the German Lymphoma Study Group sought to confirm the impact of chemoimmunotherapy specifically on the PMBCL subset of patients who were enrolled on their MiNT trial (MabThera (Rituximab) International Trial). [28]

In this trial, patients were younger than 60 years with DLBCL and had 0-1 risk factors according to the age-adjusted International Prognostic Index (aaIPI). Patients were randomly assigned to 6 cycles of CHOP-like regimens with or without rituximab. Consolidating XRT was given to sites of primary bulky disease. Of 824 patients enrolled, 87 had PMBCL. Rituximab increased the rates of complete remission (unconfirmed) in PMBCL (from 54% to 80%; P =.015). In PMBCL, rituximab virtually eliminated progressive disease (2.5% vs 24%; P =.006).With a median observation time of 62 months for PMBCL, the 5-year event-free survival was improved (79.1% vs 47.3%; P =.011). Furthermore, 5-year progression-free survival was improved by rituximab (89.8% vs 60.1%; P =.006). These data further confirmed that the addition of rituximab to 6 cycles of CHOP-likechemotherapy improved long-term outcome for young patients with PMBCL.

Multiple analyses have indicated an improvement in PMBCL outcomes when rituximab is added to a polychemotherapy backbone. This, coupled with concern regarding long‐term sequelae of RT, have led to questions about the utility of radiotherapy when rituximab is added to standard chemotherapy. A National Cancer Database (NCDB) study of 465 patients receiving multiagent chemotherapy in 2006-2011 were with a median follow‐up of 36 months demonstrated that the use of radiation therapy as a component of combined modality therapy was associated with a significant improvement in overall survival (56% reduction in hazard for death on multivariate analysis) when compared with systemic therapy alone in the years following rituximab approval. 5‐year overall survival (OS) for the entire cohort was 87%.  Patients who received radiation therapy (RT) had an OS of 93% compared to an OS of  83% among those who did not receive RT.  Although the lack of specific chemotherapy data is a limitation of the study, the data does supports the use of RT in all PMBCL stages. [29]

Patients should be evaluated clinically and radiographically to assure continued response. Interim positron emission tomography (PET) scan evaluation is discussed separately below. Patients usually undergo 6 cycles of CHOP-R administered every 3-weeks. The regimen has expected adverse effects and toxicities as discussed below, and the use of growth factors (filgrastim or peg-filgrastim) is dependent on the patient's age and comorbidities. Given the relatively younger age at PMBCL presentation, the authors advocate against the routine use of growth factors as primary prophylaxis. Secondary prophylaxis, however, is recommended to ensure adequate dose density and intensity.

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