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Loncastuximab tesirine-lpyl (ADC Therapeutics), an anti-CD19 antibody-drug conjugate, was recently approved for the treatment of relapsed, refractory diffuse large B-cell lymphoma on the basis of the results of a phase II clinical trial, LOTIS-2. Preclinical data demonstrated the selectivity and efficacy of the drug through in vitro and in vivo models. A phase I clinical trial included relapsed, refractory B-cell non-Hodgkin lymphoma (NHL) and demonstrated a tolerable safety profile, with major adverse effects being neutropenia, thrombocytopenia and elevated gamma-glutamyl transferase (GGT). A dose of 150 μg/kg intravenously every 3 weeks for two cycles followed by 75 μg/kg every 3 weeks was chosen for further testing. The phase II trial, LOTIS-2, recruited relapsed, refractory diffuse large B-cell lymphoma patients and demonstrated no new safety concerns. Overall response rate was 48.3% (24.1% CR), and OS was 9.9 months. Currently, several ongoing clinical trials are evaluating the safety and efficacy of loncastuximab tesirine in a variety of NHL subtypes., (Copyright 2021 Clarivate Analytics.)

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.