State of the art in the diagnosis, biology and treatment of primary mediastinal B-cell lymphoma: a review
Vincent Camus, Fanny Drieux, Fabrice Jardin
Abstract
Abstract: Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive large B-cell lymphoma (LBCL), representing approximately 2–4% of newly diagnosed non-Hodgkin lymphomas (NHL) and having many biological and clinical features that separate PMBL from diffuse large B-cell lymphoma (DLBCL). It typically affects young females (median age 37 years) with onset of a large and compressive anterior mediastinal mass. Several teams have highlighted the biological complexity of PMBL and contributed to building the concept that PMBL tumors possess a singular immune escape profile. The remarkable prognosis of patients treated with curative intention is a particular feature of PMBL, with a survival rate greater than 80% at 5 years in most reports. However, the therapeutic standard of care in the frontline and relapsed/refractory settings remains debated. Therapeutic options include standard rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), dose-dense immunochemotherapy with rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone (R-ACVBP) or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R), with or without consolidation radiotherapy (CRT). The place of positron emission tomography (PET)-driven treatment and autologous stem cell transplantation (ASCT) consolidation in the frontline setting also remain a subject of debate. Interpreting PET images of PMBL patients is very difficult due to the presence of inflammatory phenomena in the mediastinum under chemotherapy and after the end of the treatment regimen. These false PET-positive residual uptakes may prompt physicians to perform intensive consolidation and/or CRT, resulting in high rates of unnecessary ASCT and CRT in PMBL patients. Emerging data suggest that, in addition to PET, circulating tumor DNA (ctDNA) might be an interesting tool for the assessment of minimal residual disease (MRD) in PMBL. In the present review, we will discuss pathobiology, diagnostic spectrum, genomics, clinical issues in the treatment and prognosis of PMBL to establish unmet medical needs related to this rare condition and to help the community by describing innovative support and research. We also provide future directions for PMBL management and a rationale for the use of ctDNA monitoring in PMBL patients.