|Other names||ADCT-402, loncastuximab tesirine-lpyl|
|Chemical and physical data|
|Molar mass||147481.45 g·mol−1|
Loncastuximab tesirine, sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma and high-grade B-cell lymphoma. It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.
The most common side effects include increased levels of gamma-glutamyltransferase (GGT, a liver enzyme), neutropenia (low levels of neutrophils, a type of white blood cell), tiredness, anemia (low levels of red blood cells), thrombocytopenia (low levels of blood platelets), nausea (feeling sick), peripheral edema (swelling due to fluid retention, especially of the ankles and feet) and rash.
Loncastuximab tesirine was approved for medical use in the United States in April 2021, and in the European Union in December 2022. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.
The humanized monoclonal antibody is stochastically conjugated via a valine-alanine cleavable, maleimide linker to a cytotoxic (anticancer) pyrrolobenzodiazepine (PBD) dimer.[medical citation needed] The antibody binds to CD19, a protein which is highly expressed on the surface of B-cell hematological tumors including certain forms of lymphomas and leukemias.[medical citation needed] After binding to the tumor cells the antibody is internalized, the cytotoxic drug PBD is released and the cancer cells are killed.[medical citation needed] PBD dimers are generated out of PBD monomers, a class of natural products produced by various actinomycetes. PBD dimers work by crosslinking specific sites of the DNA, blocking the cancer cells’ division that cause the cells to die.[medical citation needed] As a class of DNA-crosslinking agents they are significantly more potent than systemic chemotherapeutic drugs.
Two phase I trials are evaluating the medication in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma and relapsed or refractory B-cell acute lymphoblastic leukemia. At the 14th International Conference on Malignant Lymphoma interim results from a Phase I, open-label, dose-escalating study designed to evaluate the treatment of loncastuximab tesirine in relapsed or refractory non-Hodgkin’s lymphoma were presented. Among the patients enrolled at the time of the data cutoff the overall response rate was 61% in the total patient population (42% complete response and 19% partial response) and in patients with relapsing or refractory diffuse large B-cell lymphoma (DLBCL) the overall response rate was 57% (43% complete response and 14% partial response).
Society and culture
On 15 September 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zynlonta, intended for the treatment of adults with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL). The applicant for this medicinal product is ADC Therapeutics (NL) B.V. Loncastuximab tesirine was approved for medical use in the European Union in December 2022.
Given its mechanism of action, loncastiximab tesirinine may be appealing in patients ineligible for CAR-T cell therapy.
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- Clinical trial number NCT02669017 for "ADCT-402 in B-NHL" at ClinicalTrials.gov
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- Perrone, Salvatore; Lopedote, Paolo; Levis, Mario; Di Rocco, Alice; Smith, Stephen Douglas (21 February 2022). "Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy". Expert Review of Hematology. 15 (3): 215–232. doi:10.1080/17474086.2022.2044778. ISSN 1747-4086. PMID 35184664. S2CID 247010986.
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- Clinical trial number NCT03589469 for "Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (LOTIS-2)" at ClinicalTrials.gov