Gene:
TNFRSF8
tumor necrosis factor receptor superfamily, member 8

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

Alternate Names:  CD30; D1S166E
Alternate Symbols:  CD30 (previous symbol); KI-1
PharmGKB Accession Id: PA36616

Details

Cytogenetic Location: chr1 : p36.22 - p36.22
GP mRNA Boundary: chr1 : 12123434 - 12204264
GP Gene Boundary: chr1 : 12113434 - 12207264
Strand: plus

Visualization

UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.
No related genes are available

Curated Information ?

Curated Information ?

Publications related to TNFRSF8: 3

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Predictive value of cytokines and immune activation biomarkers in AIDS-related non-Hodgkin lymphoma treated with rituximab plus infusional EPOCH (AMC-034 trial). Clinical cancer research : an official journal of the American Association for Cancer Research. 2015. Epeldegui Marta, 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
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

NCBI Gene:
943
OMIM:
153243
UCSC Genome Browser:
NM_001243
RefSeq RNA:
NM_001243
NM_152942
RefSeq Protein:
NP_001234
NP_694421
RefSeq DNA:
NT_021937
UniProtKB:
TNR8_HUMAN (P28908)
Ensembl:
ENSG00000120949
GenAtlas:
TNFRSF8
GeneCard:
TNFRSF8
MutDB:
TNFRSF8
ALFRED:
LO056062T
HuGE:
TNFRSF8
Comparative Toxicogenomics Database:
943
ModBase:
P28908
HumanCyc Gene:
HS04456
HGNC:
11923

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