Loncastuximab tesirine

Loncastuximab tesirine
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetCD19
Names
Pronunciation/ˌlɒnkæsˈtʌksɪmæb.ˈtɛsɪriːn/
LON-kas-TUK-si-mab TE-si-reen
Trade namesZynlonta
Other namesADCT-402, loncastuximab tesirine-lpyl
Clinical data
Routes of
use		Intravenous
External links
AHFS/Drugs.comMonograph
US NLMLoncastuximab tesirine
Legal
License data
Legal status
Chemical and physical data
FormulaC6544H10048N1718O2064S52
Molar mass147481.45 g·mol−1

Loncastuximab tesirine , sold under the brand name Zynlonta, is a medication used to treat large B-cell lymphoma.[1] It is used when other treatments have failed.[1] It is given by injection into a vein.[1]

Common side effects include low platelets, liver inflammation, low white blood cells, low red blood cells, high blood sugar, rash, swelling, and nausea.[1] Other side effects may include infection.[1] Use in pregnancy may harm the baby.[1] It is an antibody-drug conjugate composed of a monoclonal antibody targeting the protein CD19 attached to an alkylating agent.[1]

Loncastuximab tesirine was approved for medical use in the United States in 2021.[1] As of 2022 it is not yet approved in the United Kingdom or Europe.[2] In the United States it costs about 25,500 USD per 10 mg vial as of 2022.[3]

Medical uses

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

Dosage

It is given at a dose of 0.15 mg/kg every 3 weeks, twice, and than given at a dose of 0.075 mg/kg every 3 weeks.[1]

Mechanism of action

The humanized monoclonal antibody is stochastically conjugated via a valine-alanine cleavable, maleimide linker to a cytotoxic (anticancer) pyrrolobenzodiazepine (PBD) dimer. The antibody binds to CD19, a protein which is highly expressed on the surface of B-cell hematological tumors[4] including certain forms of lymphomas and leukemias. After binding to the tumor cells the antibody is internalized, the cytotoxic drug PBD is released and the cancer cells are killed. 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. As a class of DNA-crosslinking agents they are significantly more potent than systemic chemotherapeutic drugs.[5]

History

Loncastuximab tesirine was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma.[6]

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).[7] The applicant for this medicinal product is ADC Therapeutics (NL) B.V.[7]

Research

Given its mechanism of action, loncastiximab tesirinine may be appealing in those ineligible for CAR-T cell therapy.[8]

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.[9] 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.[10] 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).[11][12]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Zynlonta- loncastuximab tesirine injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 2 June 2021. Retrieved 1 June 2021.
  2. ↑ "Loncastuximab tesirine". SPS - Specialist Pharmacy Service. 1 January 2021. Archived from the original on 27 November 2021. Retrieved 30 October 2022.
  3. ↑ "Zynlonta Prices, Coupons, Copay & Patient Assistance". Drugs.com. Retrieved 30 October 2022.
  4. ↑ 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.
  5. ↑ "Pyrrolobenzodiazepine". ADC Review. Archived from the original on 2017-08-02. Retrieved 2017-08-02.
  6. ↑ "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.
  7. 1 2 "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.
  8. ↑ Perrone, Salvatore; Lopedote, Paolo; Levis, Mario; Di Rocco, Alice; Smith, Stephen Douglas (2022-02-21). "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.
  9. ↑ Clinical trial number NCT02669017 for "ADCT-402 in B-NHL" at ClinicalTrials.gov
  10. ↑ 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.{{cite journal}}: CS1 maint: url-status (link)
  11. ↑ "First clinical results of ADCT-402". ADC Review. 16 June 2017. Archived from the original on 2 August 2017. Retrieved 2 August 2017.
  12. ↑ 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.
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