Biology and therapy of primary mediastinal B‐cell lymphoma: current status and future directions

Abstract

Summary Primary mediastinal B‐cell lymphoma ( PMBCL ) is a distinct disease closely related to classical nodular sclerosing Hodgkin lymphoma. Conventional diagnostic paradigms utilising clinical, morphological and immunophenotypical features can be challenging due to overlapping features with other B‐cell lymphomas. Reliable diagnostic and prognostic biomarkers that are applicable to the conventional diagnostic laboratory are largely lacking. Nuclear factor kappa B ( NF ‐κB) and Janus kinase/signal transducers and activators of transcription ( JAK ‐ STAT ) signalling pathways are characteristically dysregulated in PMBCL and implicated in several aspects of disease pathogenesis, and the latter pathway in host immune evasion. The tumour microenvironment is manipulated by PMBCL tumours to avoid T‐cell mediated destruction via strategies that include loss of tumour cell antigenicity, T‐cell exhaustion and activation of suppressive T‐regulatory cells. R‐ CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and DA ‐ EPOCH ‐R (dose‐adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab) are the most common first‐line immunochemotherapy regimens. End of treatment positron emission tomography scans are the recommended imaging modality and are being evaluated to stratify patients for radiotherapy. Relapsed/refractory disease has a relatively poor outcome despite salvage immunochemotherapy and subsequent autologous stem cell transplantation. Novel therapies are therefore being developed for treatment‐resistant disease, targeting aberrant cellular signalling and immune evasion.

How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation

“…Therefore, R-CHOP followed by radiotherapy is still an accepted therapy. 12 Other aggressive lymphomas in which the practice should not be changed include: Burkitt's lymphoma, plasmablastic lymphoma and lymphoblastic lymphoma. These are highly aggressive lymphomas that require immediate treatment due to the risk of life-threatening complications.…”

Nivolumab plus gemcitabine, dexamethasone, and cisplatin chemotherapy induce durable complete remission in relapsed/refractory primary mediastinal B-cell lymphoma: a case report and literature review

“…Unlike other lymphomas, prognostic biomarkers are largely lacking in PMBCL. 12 Some serum molecules, such as CCL17 and CD163, are considered as potential biomarkers for predicting and monitoring responses and detection of relapses in patients with Hodgkin lymphoma. 12,21 The role of serum biomarkers in PMBCL remains to be investigated.…”

Treatment of relapsed/refractory paediatric aggressive B‐cell non‐Hodgkin lymphoma

“…Primary mediastinal B‐cell lymphoma is a unique clinical and biologic entity, with a peak incidence in the AYA population. It is distinct from other B‐cell NHL subtypes and has features that overlap with classic Hodgkin lymphoma including biologic similarities, such as immune evasion and constitutive activation of the JAK‐STAT and NF‐kB pathways (Swerdlow et al , 2016; Lees et al , 2019). Second‐line strategies for r/r PMBCL both in children and in adults have been similar to those used in r/r B‐NHL, including salvage programmes with non‐cross‐resistant agents such as rituximab plus ICE or DHAP or the less toxic R‐GDP (rituximab, gemcitabine, dexamethasone, cisplatin) followed by consolidation high‐dose therapy and autologous HSCT.…”