Introduction: Approximately, a third of patients with diffuse large B-cell lymphoma (DLBCL) have refractory or relapsed disease after initial treatment. Despite recent regulatory approval of several new agents, including CAR-T cell therapy, polatuzumab vedotin and tafasitamab, there is still a need for additional therapies that expand the therapeutic alternatives and improve outcomes for patients with DLBCL that progresses after first line therapy., Areas Covered: Studies of recently approved agents for relapsed DLBCL are reviewed. The relevance of CD19 as an immunotherapeutic target. The pharmacologic composition of loncastuximab tesirine and its cytotoxic payload, a pyrrolobenzodiazepine dimer. Phase I and phase 2 data for loncastuximab tesirine in non-Hodgkin lymphoma, showing the safety profile of this drug and the emerging efficacy results in DLBCL., Expert Opinion: Loncastuximab tesirine is an antiCD19 antibody drug conjugate with a novel cytotoxic payload. Early studies showed this drug is tolerable, with a safety profile that is different from other antibody drug conjugates approved for lymphoid malignancies. Efficacy data shows activity in different non-Hodgkin lymphoma entities, and a phase 2 study has been completed in DLBCL showing durable responses, including in high-risk subgroups. Loncastuximab tesirine will be an important addition to the treatment alternatives for DLBCL.