Introduction: Double hit lymphoma (DHL) represents a new diagnostic category with genetic, immunohistochemical and clinical characteristics intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Patients with DHL usually experience poor survival after frontline R-CHOP treatment and require alternative therapies. However, the ideal therapeutic options remain undefined. Areas covered: Traditional therapies for the treatment of DHL are discussed, including intensive induction, hematopoietic stem cell transplantation (HSCT), methotrexate CNS-directed prophylaxis, and radiation therapy. The authors further introduce small-molecule inhibitors targeting myc or bcl-2 signaling pathways, chimeric antigen receptor T-cell therapy, programmed death-1 monoclonal antibody and immunomodulatory drugs as novel approaches. Expert opinion: No standard treatment exists for DHL. At present, DA-EPOCH-R exhibits an upfront induction option. Central nervous system prophylaxis with methotrexate is recommended as part of the induction therapy. For those who do not obtain complete remission, HSCT or clinical trials should be considered. Targeted approaches, especially chimeric antigen receptor T-cell therapies and small-molecule inhibitors targeting myc or bcl-2, exhibit the potential of improving outcomes for patients with DHL. High-throughput sequencing is a promising technique both at diagnosis and relapse, in order to predict outcomes and potential novel therapies.
Keywords: Double hit lymphoma; chimeric antigen receptor T-cell therapy; hematopoietic stem cell transplantation; high-throughput sequencing; targeted therapy.