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Drugs of interest to pathologists

Drugs related to clinical pathology

Sipuleucel-T


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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● Autologous cellular immunotherapy agent (vaccine)

Trade name
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● Provenge®

Clinical information
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● Approved by US Food and Drug Administration for asymptomatic or minimally symptomatic metastatic hormone-refractory prostatic carcinoma
● Cost is $93,000 for 3 infusions
● Medicare may provide full coverage

Proposed mechanism of action
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● The precise mechanism of action is unknown
● Developed based on concept of antigen-presenting cells (APCs), which include dendritic cells, macrophages and B lymphocytes
● APCs can internalize, process and present antigens on their cell surface, where they are recognized by T cell receptors
● APCs express major histocompatibility (MHC) class II molecules, which can stimulate CD4+ T helper cells and MHC class I molecules, which can stimulate CD8+ T cytotoxic cells
● APCs from patients blood are harvested by leukapheresis, sent to drug company (Dendreon), where they are incubated with recombinant fusion protein antigen containing PAP (prostatic acid phosphatase) and GM-CSF (granulocyte-macrophage colony-stimulating factor)
● These antigen-loaded APCs are infused into patient, and may prime a T-cell mediated immune response against prostatic cancer cells (J Clin Oncol 2006;24:3089)


Proposed mechanism of action (from manufacturer's website)

Drug administration features
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● Complete process takes up to four days from leukapheresis
● Course of therapy consists of three complete doses given at 2 week intervals
● Maximum dosing interval has not been established
● If patient is unable to receive a scheduled infusion, an additional leukapheresis procedure is necessary to continue the course of treatment
● Each dose contains a minimum of 50 million autologous CD54+ cells containing PAP-GM-CSF suspended in 250 ml lactated Ringerís solution USP; is infused within 60 minutes
● Patient identifiers and expiration date must be checked before infusion
● Product is tested by manufacturer by Gram stain, endotoxin content and in-process sterility with two-day incubation, but final sterility tests are not available at time of infusion
● Manufacturer notifies treating physician if sterility results become positive after the drug has been approved for infusion (P T 2010;35:345)
● Bag content is normally slightly cloudy with a cream to pink color; small clumps should disperse with gentle mixing; do NOT use if lumps do not disperse after gentle mixing or if bag has a leak
● Insultate the bag in polyurethane until time of infusion
● Discard if bag is left at room temperature for >3 hours (Provenge, Dendreon, prescribing information)
● Use universal precautions during handling of leukapheresis material and sipuleucel-T, since they product is not routinely tested for transmissible infectious diseases
● Most common adverse effects are acute infusion reactions of fever, chills, dyspnea
● If acute infusion reaction occurs, can decrease / stop infusion, depending on severity of the reaction
● Can premedicate with acetaminophen and antihistamines 30 minutes before infusion to prevent some of these reactions (N Engl J Med 2010;363:411)
● No studies of drug interactions with sipuleucel-T have been performed (P T 2011;32:197)
● The use of chemotherapy (e.g. docetaxel) or immunosuppressive agents (e.g. corticosteroids) given concurrently with sipuleucel-T has not been studied

End of Drugs > Drugs related to clinical pathology > Sipuleucel-T


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