Primary Mediastinal B-Cell Lymphoma: Novel Precision Therapies and Future Directions

Abstract

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinicopathologic disease from other types of diffuse large B-cell lymphoma (DLBCL) with unique prognostic features and limited availability of clinical data. The current standard treatment for newly diagnosed PMBCL has long been dependent on a dose-intensive, dose-adjusted multi-agent chemotherapy regimen of rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Recent randomized trials have provided evidence that R-CHOP followed by consolidation radiotherapy (RT) is a valuable alternative option to first-line treatment. For recurrent/refractory PMBCL (rrPMBCL), new drugs such as pembrolizumab and CAR-T cell therapy have proven to be effective in a few studies. Positron emission tomography-computed tomography (PET-CT) is the preferred imaging modality of choice for the initial phase of lymphoma treatment and to assess response to treatment. In the future, baseline quantitative PET-CT can be used to predict prognosis in PMBCL. This review focuses on the pathology of PMBCL, underlying molecular basis, treatment options, radiotherapy, targeted therapies, and the potential role of PET-CT to guide treatment choices in this disease.

Refractory Primary Mediastinal B-Cell Lymphoma: A Case Report of Conventional Chemotherapies, Immune Checkpoint Inhibitors, Polatuzumab Vedotin, Transplantation, and Post-Transplant Large Granular Lymphocytosis

“…9 In an NCI (National Cancer Institute, USA) study evaluating the role of CAR-T therapy in R/R B-cell lymphoma, of the four patients with R/R PMBCL, two (50%) had CR and one (25%) had stable disease. 4 Our patient received an accepted upfront therapy for PMBCL that was followed by an early relapse. She thereafter received sequential lines of therapy that included conventional chemotherapy, immune checkpoint inhibitor-based treatment, and immunomodulatory therapy.…”

“…9 In an NCI (National Cancer Institute, USA) study evaluating the role of CAR-T therapy in R/R B-cell lymphoma, of the four patients with R/R PMBCL, two (50%) had CR and one (25%) had stable disease. 4…”

“…The outcomes of the latter condition are poor. 4 Relapse generally occurs in the initial 12 months, is more likely to be widespread, and can involve the central nervous system (CNS). Once relapsed or progressive disease, the median overall survival is ∼16 months.…”

Immune Checkpoint Inhibitors in Hodgkin Lymphoma and Non-Hodgkin Lymphoma

“…However, more than 10% of patients still suffered relapsed or refractory, and the outcomes in r/r PMBCL remain poor. Studies have elucidated that PMBCL shared many similar biological features with cHL, including the importance of JAK-STAT and NF-κB signaling pathways as well as immune evasion [141]. Aberration expressions of PD-L1 and PD-L2 were found in PMBCL tumors, and the efficacy of anti-PD-1 antibody (pembrolizumab) in r/r PMBCL was confirmed in phase 1 KEYNOTE-013 study [142].…”

Biochemical, Enzymatic, and Computational Characterization of Recurrent Somatic Mutations of the Human Protein Tyrosine Phosphatase PTP1B in Primary Mediastinal B Cell Lymphoma

“…Primary mediastinal B cell lymphoma (PMBCL) is a rare subtype of aggressive B cell lymphoma that is putatively derived from thymic B cells [1]. Although PMBCL is considered distinct from other B cell non-Hodgkin lymphoma subtypes, it has features that overlap with Hodgkin lymphoma [1]. The malignant cells express B cell markers (CD19, CD20, CD22) and B cell transcription factors such as PAX5, OCT2, and BCL6 [2].…”