Loncastuximab Tesirine: First Approval

Loncastuximab tesirine (loncastuximab tesirine-lpyl; ZYNLONTA™) is an antibody-drug conjugate being developed for the treatment of B cell lymphomas by ADC Therapeutics SA. Loncastuximab tesirine consists of a pyrrolobenzodiazepine DNA-alkylating warhead covalently attached via a cleavable linker to an anti-CD19 antibody that binds to B cells. It is currently approved in the US for the treatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL), and is being developed for the treatment of mantle-cell lymphoma, follicular lymphoma and acute lymphoblastic leukaemia. This article summarizes the milestones in the development of loncastuximab tesirine leading to this first approval for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified (NOS), DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.