Chemical: Drug
brentuximab vedotin

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


Annotated Labels

  1. FDA Label for brentuximab vedotin and TNFRSF8
  2. EMA Label for brentuximab vedotin and TNFRSF8

last updated 10/25/2013

1. FDA Label for brentuximab vedotin and TNFRSF8

Informative PGx

Summary

Brentuximab vedotin (Adcetris) is an antibody-drug conjugate (ADC) directed at TNFRSF8 (CD30), and nonclinical data suggests its anti-cancer mechanism of action is by binding to CD30-expressing cells and then releasing a small molecule that disrupts microtubules.

Annotation

Brentuximab vedotin (Adcetris) is indicated in patients with Hodgkin lymphoma or systemic anaplastic large cell lymphoma after at least one treatment failure.

Excerpt from the brentuximab vedotin (Adcetris) drug label:

12.1 Mechanism of Action
Brentuximab vedotin is an ADC. The antibody is a chimeric IgG1 directed against CD30. The small molecule, MMAE, is a microtubule disrupting agent. MMAE is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of ADCETRIS is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC-CD30 complex, and the release of MMAE via proteolytic cleavage. Binding of MMAE to tubulin disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptotic death of the cells.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the brentuximab (Adcentris) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Former FDA Biomarker

This label used to be included on the FDA biomarker list and has since been removed. The PharmGKB curation staff monitors the FDA biomarker list on a regular basis and notes removals. There is no official list of removals supplied by the FDA.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • CYP3A4
    • metabolism/PK, Drug interactions section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration
  • CYP3A5
    • metabolism/PK, Drug interactions section, Pharmacokinetics section
    • source: U.S. Food and Drug Administration
  • TNFRSF8
    • other, Indications & usage section, Description section, Clinical pharmacology section, Mechanism of action section
    • source: U.S. Food and Drug Administration

last updated 10/25/2013

2. EMA Label for brentuximab vedotin and TNFRSF8

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) contains information regarding the indication of brentuximab vedotin in patients with CD30-expressing tumour cells due to the drug's mechanism of action.

Annotation

Excerpt from the brentuximab vedotin (Adcetris) EPAR:

ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL).


Mechanism of action
Brentuximab vedotin is an antibody drug conjugate (ADC) that delivers an antineoplastic agent that results in apoptotic cell death selectively in CD30-expressing tumour cells. Nonclinical data suggest that the biological activity of brentuximab vedotin results from a multi-step process. Binding of the ADC to CD30 on the cell surface initiates internalisation of the ADC-CD30 complex, which then traffics to the lysosomal compartment. Within the cell, a single defined active species, MMAE, is released via proteolytic cleavage. Binding of MMAE to tubulin disrupts the microtubule network within the cell, induces cell cycle arrest and results in apoptotic death of the CD30-expressing tumour cell. Classical HL and sALCL express CD30 as an antigen on the surface of their malignant cells. This expression is independent of disease stage, line of therapy or transplant status. These features make CD30 a target for therapeutic intervention.

This information is highlighted in the following sections:
Qualitative and quantitative composition, Therapeutic indications, Pharmacodynamic properties, Package leaflet: Information for the patient.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the brentuximab vedotin EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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Overview

Generic Names
  • 124490327
  • SGN-35
  • brentuximab vedotin
Trade Names
  • Adcetris
Brand Mixture Names

PharmGKB Accession Id

PA165948903

Type(s):

Drug

Description

Brentuximab vedotin is comprised of an anti-CD30 monoclonal antibody linked to a potent cell-killing agent, monomethyl auristatin E (MMAE). The conjugate is designed to be stable in the bloodstream, but to release MMAE, an antimicrotubule agent, upon internalization into CD30-expressing tumor cells, resulting in a targeted cell-killing effect.

Source: PharmGKB [Article:25200691]

Indication

Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30. Systemic ALCL is an aggressive type of T-cell non-Hodgkin lymphoma (NHL) that also expresses CD30.

Source: PharmGKB

Other Vocabularies

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A5
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
TNFRSF8

Drug Targets

Gene Description
TNFRSF8 [PMID: 25200691] (source: PharmGKB)
No related drugs are available.
No related diseases are available

Publications related to brentuximab vedotin: 2

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Brentuximab vedotin for treatment of systemic T-cell lymphoma. Expert opinion on biological therapy. 2014. Chihara Dai, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al. PubMed

LinkOuts

PubChem Substance:
124490327
131277422

Clinical Trials

These are trials that mention brentuximab vedotin and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.