Loncastuximab tesirine (Zynlonta)

Mechanism of action

From the NCI Drug Dictionary: An antibody-drug conjugate (ADC) consisting of an anti-CD19 humanized monoclonal antibody conjugated, via a cleavable linker comprised of valine-alanine and maleimide, to a cytotoxic, cross-linking agent pyrrolobenzodiazepine (PBD) dimer, which targets DNA minor grooves, with potential antineoplastic activity. Upon administration, the monoclonal antibody portion of loncastuximab tesirine targets the cell surface antigen CD19 on various cancer cells. Upon antibody/antigen binding and internalization, the cytotoxic PBD moiety is released. The imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links in the minor groove of DNA and inhibits DNA replication, which inhibits the proliferation of CD19-overexpressing tumor cells.

Diseases in which it is used

• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Transformed lymphoma

History of changes in FDA indication

• 2021-04-23: Granted accelerated approval for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. (Based on LOTIS-2)

History of changes in EMA indication

• 2022-12-20: Granted conditional authorization as monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy.

Also known as

• Code name: ADCT-402
• Generic name: loncastuximab tesirine-lpyl
• Brand name: Zynlonta