Advances in Immunotherapy for Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that is normally treated with combination chemotherapy combined with the anti-CD20 monoclonal antibody rituximab. Although about two-thirds of patients are cured with initial chemo-immunotherapy, a sizable minority of patients will have relapsed or refractory (r/r) DLBCL. Standard therapy for r/r DLBCL is salvage chemotherapy followed by autologous stem cell transplantation (ASCT); however, a minority of patients have long-term remission with this approach. In recent years, there has been a proliferation of immunotherapies for the treatment of DLBCL that have expanded our treatment options for these patients, providing the opportunity for durable remissions that were not previously possible. In this review, we discuss these novel immunotherapies, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies and chimeric antigen receptor (CAR) T cells. The plethora of novel agents leaves patients with more therapeutic options, but leaves the practitioner faced with challenging decisions regarding the timing and indications for use of these immunotherapies. Although studies are ongoing, no agents have been verified as alternatives to standard salvage therapy followed by ASCT at first relapse. The opportunity for durable response and broad age range eligibility makes a strong case for CAR T cells to be used as third-line therapy. The remainder of the agents discussed can be useful in specific clinical scenarios including in patients who are not candidates for ASCT or CAR T cells, as bridging therapy to CAR T cells, or in the r/r setting after CAR T cell therapy failure.