Emerging Biological Insights and Novel Treatment Strategies in Primary Mediastinal Large B-Cell Lymphoma

While primary mediastinal large B-cell lymphoma (PMBCL) is considered to be a subtype of diffuse large B-cell lymphoma, it is a distinct clinicopathologic entity, with clinical and biological features closely resembling nodular sclerosing Hodgkin lymphoma. Recent studies have highlighted the shared biology of these two entities and identified novel critical pathways of lymphomagenesis, including the presence of distinct mutations. Mediastinal grey zone lymphomas with features in between PMBCL and nodular sclerosing Hodgkin lymphoma have been described as the missing link between the two parent entities. While the standard therapeutic approach to PMBCL has been immunochemotherapy followed by mediastinal radiation, strategies that obviate the need for radiation and thus eliminate its long-term toxicities have recently been developed. The identification of novel targets in PMBCL and mediastinal grey zone lymphomas have paved the way for testing of agents such as small molecule inhibitors of Janus kinase pathways and immune checkpoint inhibitors. Future directions in these diseases should focus on combining effective novel agents with immunochemotherapy platforms.