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Drugs of interest to pathologists

Drugs related to surgical pathology

Brentuximab vedotin


Author: Him G. Kwee, M.D. (see Reviewers/Authors page)
Revised: 19 January 2012, last major update January 2012
Copyright: (c) 2012, PathologyOutlines.com, Inc.

General
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● A monoclonal antibody-drug conjugate targeting CD30 (cell membrane protein)

Trade name
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● Adcetris®

Clinical information
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Approved by US Food and Drug Administration on August 19, 2011 for:
● Hodgkin lymphoma after failure of autologous stem cell transplant or after at least two prior treatments with multi-agent chemotherapy regimens and the patient is not a candidate for an autologous stem cell transplant
● Systemic anaplastic large-cell lymphoma (ALCL) after failure with at least one prior treatment with a multi-agent chemotherapy regimen (National Cancer Institute, Cancer Drug Information, August 19, 2011)

● Cost is $4500 per vial; one dose is 3 vials
● The average patient may need 7 to 9 doses (Reuters, August 22, 2011), for a projected cost of ~ $100,000

Drug administration
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● Brentuximab vedotin consists of a chimeric (mouse/human) IgG1 monoclonal antibody that targets CD30; the antibody is attached by an enzyme-cleavable linker to a synthetic anti-mitotic agent, MMAE (monomethyl auristatin E)
● The drug is given intravenously and is stable in the bloodstream, but after internalization by CD30+ tumor cells, MMAE is released and inhibits mitosis of the tumor cells (Blood 2003;102:1458)
● Has been used for ALK+ anaplastic large cell lymphoma, as well as ALK- cases
● Since MMAE is an anti-tubulin agent inhibiting microtubular function, it can cause peripheral neuropathy
● Other side effects: neutropenia, tumor lysis syndrome, Stevens-Johnson syndrome, progressive multifocal leukoencephalopathy, fatigue or infusion reactions (N Engl J Med 2010;363:1812)

End of Drugs > Drugs related to surgical pathology > Brentuximab vedotin


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