The role of novel immunotherapies in non-Hodgkin lymphoma

Immunotherapy is an evolving modality in the treatment of non-Hodgkin lymphoma. Vaccinations with patient-specific tumor-derived antigens have been developed to strengthen immune response to tumor. The success of rituximab, a monoclonal antibody for CD20 on malignant B-cells, fueled further immunotherapy research. The power of the immune system to fight hematologic malignancies is seen in allogeneic stem cell transplant, where donor T cells attack residual malignant cells in the recipient. Now, three innovative therapeutic immunotherapy classes (I) adoptive cellular therapy; (II) immunecheckpoint inhibitors; and (III) novel antibody therapies show promising results in non-Hodgkin lymphoma. Genetically engineered T cells, CAR T cells, obtained remissions in lymphomas refractory to conventional chemotherapy. Immune-checkpoint inhibitors, such as nivolumab and pembrolizumab revolutionized the treatment of many solid tumors, and unprecedented results are now reported in relapsed/refractory lymphoma. Building on the success of rituximab, additional therapeutic monoclonal antibodies were developed for lymphoma treatment. Antibodies have recently been further engineered with multiple binding sites to directly engage both tumor and T cells. There are exciting early clinical trial results for the first bispecific T-cell engager (BiTE), blinatumomab, as well as promising ongoing studies for dual antibody molecules, Dual-Affinity Re-Targeting (DART) proteins. This review highlights these three immunotherapy classes for relapsed/refractory non-Hodgkin lymphomas and discusses the mechanism of action, clinical efficacy, and toxicities of each.