Manufacturer:

Dendreon Corporation

Pharmacological Class:

Autologous cellular immunotherapy.

Active Ingredient(s):

Sipuleucel-T (autologous CD54+ cells activated with PAP-GM-CSF); minimum 50 million cells/dose; suspension for IV infusion.

Indication(s):

Asymptomatic or minimally symp­tomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

Pharmacology:

Sipuleucel-T is an autologous cellular immunotherapy designed to induce an immune ­response targeted against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers. During ex vivo culture with PAP-GM-CSF, antigen-presenting cells (APCs) take up and process the recombinant target antigen into small peptides that are then displayed on the APC surface. The product consists of autologous peripheral blood mononuclear cells, including APCs, that have been activated during a defined culture period with a recombinant antigen consisting of PAP linked to an immune cell activator, granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient’s peripheral blood mononuclear cells are obtained by standard leukapheresis about 3 days before the infusion date. Both patient and physician must adhere to the personalized leukapheresis and infusion schedules.

In addition to the minimal 50 million autologous CD54+ activated cells, the product also contains T cells, B cells, natural killer cells, and others, and may contain residual amounts of intact PAP-GM-CSF.

Clinical Trials:

The effect of sipuleucel-T on patients with metastatic hormone refractory prostate cancer was studied in three similar placebo-controlled trials. After randomization, patients underwent a series of 3 leukapheresis procedures followed by an infusion of either sipuleucel-T or control (unactivated autologous peripheral mononuclear cells). After treatment, patients were followed and treated according to the discretion of their physicians.

In Study 1, 512 patients were randomized in a 2:1 ratio to receive sipuleucel-T or control. This study excluded patients with visceral metastases and moderate-to-severe cancer-related pain, and all patients had baseline testosterone levels <50ng/mL. In Study 2, a similar study in 127 patients with no cancer-­related pain, the primary endpoint was time to disease progression. Analysis of the primary endpoint did not reach statistical significance. A third study was terminated before completion of planned accrual.

For Study 1, the overall median survival for patients treated with sipuleucel-T was 25.8 months, compared to 21.7 months for control. For Study 2, the overall survival results were 25.9 months for the sipuleucel-T group and 21.4 months for the control group.

Legal Classification:

Rx

Adults:

Autologous use only. Obtain product release from manufacturer, match patient identity on product and Cell Product Disposition form, check expiration date and time on product before infusing. Premedicate 30 minutes before infusion with acetaminophen and antihistamine. Give three doses at 2-week intervals. For each dose: give entire contents of bag by IV infusion over 60 minutes; do not use filter; do not use if clumps do not disperse with gentle mixing. Observe patient for at least 30 minutes after infusion. May interrupt or slow infusion if acute transfusion reaction occurs; do not restart if product at room temp for >3 hours.

Children:

Not applicable.

Warnings/Precautions:

Cardiac or pulmonary conditions. Each dose requires a standard leukapheresis procedure about 3 days before infusion. If scheduled infusion is missed, do an additional leukapheresis procedure if treatment course is to be continued. Risk of disease transmission. Pregnancy, lactation: not applicable.

Interaction(s):

May be antagonized by concomitant ­chemotherapy or immunosuppressive therapy.

Adverse Reaction(s):

Infusion reactions (eg, chills, fever, respiratory events, GI upset, hypertension, tachycardia), fatigue, back pain, joint ache, headache.

Notes:

If product sterility tests indicate microbial contamination, manufacturer will contact physician (tests are incomplete at time of infusion).

How Supplied:

Patient-specific bag (250mL)—1

Last Updated:

10/28/2010