The Novel Therapeutic Landscape for Relapsed/Refractory Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that has been traditionally treated with anthracycline-based chemotherapy, but approximately one-third of patients relapse after first-line therapy or have primary refractoriness. In this focused review, we discuss the 7 novel Food & Drug Administration (FDA)-approved medications for relapsed/refractory (R/R) DLBCL. We describe 5 CD19-targeted therapies, 3 of which are chimeric antigen receptor (CAR)-T cell therapies. We also highlight novel non-cell-based targeted therapies and discuss optimal sequencing considerations based on the goal of treatment, with an emphasis on CAR-T cell therapy as curative intent. We consider the limited tolerability of certain novel agents, prospects for elderly patients, and financial aspects of these approaches. We discuss advantages and limitations of these targeted therapies based on seminal clinical trials. Finally, we summarize ongoing trials involving promising agents making their way into the pharmacologic pipeline. These therapies include allogeneic CAR-T treatments and multi-antigen targeting therapies such as the CD19/CD22 CAR-T and the CD3/CD20 bispecific antibodies mosunetuzumab and odronextamab. We summarize our approach based on the best available evidence as we enter 2022.