Loncastuximab tesirine

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Loncastuximab tesirine
Loncastuximab tesirine.svg
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetCD19
Clinical data
Pronunciation/ˌlɒnkæsˈtʌksɪmæb.ˈtɛsɪrn/
LON-kas-TUK-si-mab TE-si-reen
Trade namesZynlonta
Other namesADCT-402, loncastuximab tesirine-lpyl
AHFS/Drugs.comMonograph
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6544H10048N1718O2064S52
Molar mass147481.45 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.[1][2] It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.[1]

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.[2]

Loncastuximab tesirine was approved for medical use in the United States in April 2021,[1][3] and in the European Union in December 2022.[2] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[4]

Medical uses[edit]

Loncastuximab tesirine is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma and high-grade B-cell lymphoma.[1][2]

Technology[edit]

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[5] 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.[6]

History[edit]

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.[7] 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.[8] 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).[9][10]

Loncastuximab tesirine was granted orphan drug designation by the FDA for the treatment of diffuse large B-cell lymphoma.[11][4]

Society and culture[edit]

Legal status[edit]

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).[12] The applicant for this medicinal product is ADC Therapeutics (NL) B.V.[12] Loncastuximab tesirine was approved for medical use in the European Union in December 2022.[2]

Research[edit]

Given its mechanism of action, loncastiximab tesirinine may be appealing in patients ineligible for CAR-T cell therapy.[13]

References[edit]

  1. ^ a b c d e "Zynlonta- loncastuximab tesirine injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 2 June 2021. Retrieved 1 June 2021.
  2. ^ a b c d e f "Zynlonta EPAR". European Medicines Agency (EMA). 14 September 2022. Retrieved 26 January 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. ^ "Drug Approval Package: Zynlonta". U.S. Food and Drug Administration (FDA). 24 May 2021. Archived from the original on 2 June 2021. Retrieved 1 June 2021.
  4. ^ a b Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  5. ^ Wang K, Wei G, Liu D (November 2012). "CD19: a biomarker for B cell development, lymphoma diagnosis and therapy". Experimental Hematology & Oncology. 1 (1): 36. doi:10.1186/2162-3619-1-36. PMC 3520838. PMID 23210908.
  6. ^ "Pyrrolobenzodiazepine". ADC Review. Archived from the original on 2 August 2017. Retrieved 2 August 2017.
  7. ^ Clinical trial number NCT02669017 for "ADCT-402 in B-NHL" at ClinicalTrials.gov
  8. ^ Kahl B, Hamadani M, Caimi PF, Reid EG, Havenith K, He S, Feingold JM, O'Connor O (June 2017). "First clinical results of ADCT‐402, a novel pyrrolobenzodiazepine-based antibody drug conjugate (ADC), in relapsed/refractory B‐cell linage NHL" (PDF). Hematol Oncol. 35 (S2): 49–51. doi:10.1002/hon.2437_33.[permanent dead link]
  9. ^ "First clinical results of ADCT-402". ADC Review. 16 June 2017. Archived from the original on 2 August 2017. Retrieved 2 August 2017.
  10. ^ Bainbridge K (3 July 2017). "Grandfather fighting deadly cancer reveals scans of tumors after testing new drug". Mirror. Archived from the original on 28 March 2018. Retrieved 5 April 2018.
  11. ^ "Loncastuximab tesirine Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 8 June 2017. Archived from the original on 2 June 2021. Retrieved 1 June 2021.
  12. ^ a b "Zynlonta : Pending EC decision". European Medicines Agency (EMA). 15 September 2022. Archived from the original on 16 September 2022. Retrieved 18 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  13. ^ 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.

External links[edit]