Primary mediastinal large B-cell lymphoma

• We discuss key clinicopathologic and genetic features of this lymphoma.
• We discuss about the role of rituximab and PET scan.
• We have presented data to support omission of mediastinal radiation in select patients.
• Data on intensified chemotherapy alone such as DA-R-EPOCH is discussed.
• Promising targeted agents are briefly discussed.

The management of primary mediastinal large B-cell lymphoma (PMBCL) requires a balance between optimizing chances of cure and reducing risk of long-term toxicities. The combination of rituximab to cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) followed by mediastinal radiation results in a plateau in progression-free survival after first few years of follow-up. In rituximab era, a negative positron emission tomography (PET) scan performed after the completion of immunochemotherapy has a high predictive value for durable remission. Consequently, end-of-therapy PET may be utilizable to avoid radiation without compromising survival. Additionally, intensified chemotherapy alone has shown excellent survival. PMBCL is frequently associated with amplification of programmed death ligand (PDL) 1/2 and constitutive activation of JAK–STAT and NFKB pathways; these may serve as promising therapeutic targets. Clinical trials that integrate novel therapies into upfront immunochemotherapy and utilize end-of-therapy PET scan to guide mediastinal radiation have potential to further enhance survival and prevent long-term toxicities.