Provenge

Prostatic Acid Phosphatase (PAP) T-Cell Therapy

 
NOTE: Sipuleucel-T is not routinely tested for transmissable infectious diseases. Patient leukapheresis material and sipuleucel-T may carry the risk of transmitting infectious diseases to health care professionals handling the product. Employ universal precautions in handling leukapheresis material or sipuleucel-T.

Visually inspect product for particulate matter and discoloration prior to administration.

Sipuleucel-T is intended solely for autologous use. Confirm the proper product has been received according to the label on the outside of the insulated polyurethane container. Prior to infusion, match the patient's identity with patient identifiers on the Cell Product Disposition Form and the sipuleucel-T infusion bag.
Premedication with acetaminophen and an antihistamine such as diphenhydramine should be given approximately 30 minutes before each infusion to attenuate infusion-related events.
Patients require close monitoring during the infusion due to the potential for severe pulmonary and cardiovascular infusion-related reactions.
Storage: Sipuleucel-T infusion bag must remain in the insulated polyurethane container and inside the outer cardboard shipping box until the time of administration.
 
Preparation for infusion:
Each dose of sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF, suspended in 250 ml Lactated Ringer's Solution, USP in a sealed, patient-specific infusion bag.
Remove the bag from the insulated polyurethane container and inspect the bag for leaks. Do not administer if the bag leaks.
Contents of the bag will be slightly cloudy with a cream-to-pink color. Gently mix to re-suspend the contents of the bag, inspecting for clumps and clots. Small clumps of cellular material should disperse with gentle manual mixing. Do not administer if the bag leaks during handling or if clumps remain in the bag.
 
Intermittent infusion:
Infusion must begin prior to the expiration date and time indicated on the Cell Product Disposition Form and Product Label. Do not initiate infusion of expired sipuleucel-T. Sipuleucel-T is supplied in a sealed, patient-specific infusion bag.
Infuse the entire volume in the infusion bag over approximately 60 minutes. Do not use a cell filter.
Observe the patient for at least 30 minutes after the infusion is complete.
If an acute infusion reaction occurs, the infusion may be interrupted or slowed, depending on the severity of the reaction. In clinical trials, acute infusion reactions were treated with acetaminophen, intravenous H1 and/or H2 blockers, and low dose meperidine. If the infusion must be interrupted, do not resume if the sipuleucel-T is at room temperature for more than 3 hours.

stroke / Early / 3.5-3.5
infusion-related reactions / Rapid / 0.8-3.5
back pain / Delayed / 3.0-3.0
chills / Rapid / 2.2-2.2
arthralgia / Delayed / 1.8-1.8
anemia / Delayed / 1.8-1.8
dyspnea / Early / 1.8-1.8
fever / Early / 1.0-1.0
asthenia / Delayed / 1.0-1.0
fatigue / Early / 1.0-1.0
hematuria / Delayed / 1.0-1.0
headache / Early / 0.7-0.7
bone pain / Delayed / 0.7-0.7
musculoskeletal pain / Early / 0.5-0.5
myalgia / Early / 0.5-0.5
nausea / Early / 0.5-0.5
hypertension / Early / 0.5-0.5
dizziness / Early / 0.3-0.3
vomiting / Early / 0.3-0.3
hot flashes / Early / 0.3-0.3
weight loss / Delayed / 0.3-0.3
paresthesias / Delayed / 0.2-0.2
diarrhea / Early / 0.2-0.2
anorexia / Delayed / 0.2-0.2
constipation / Delayed / 0.2-0.2
peripheral edema / Delayed / 0.2-0.2
hyperhidrosis / Delayed / 0.2-0.2
bronchospasm / Rapid / Incidence not known

hypoxia / Early / Incidence not known

influenza / Delayed / 9.7-9.7
infection / Delayed / 5.5-6.3
insomnia / Early / 6.2-6.2
cough / Delayed / 5.8-5.8
rash / Early / 5.2-5.2
tremor / Early / 5.0-5.0

Provenge

Rx

Autologous cellular immunotherapy for prostate cancer; vaccine contains autologous peripheral blood mononuclear cells, including antigen presenting cells (APCs), cultured with a fusion protein which is made up of prostatic acid phosphatase fused to granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF).

Each dose of sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF suspended in 250 mL of Lactated Ringer's Injection, USP in a sealed, patient-specific infusion bag. Administer the entire contents of the bag via IV infusion over 60 minutes; give approximately every 2 weeks for 3 doses. To minimize acute infusion reactions, premedicate with acetaminophen and an antihistamine (e.g., diphenhydramine) 30 minutes prior to the infusion. If an acute infusion reaction occurs during the infusion, sipuleucel-T may need to be interrupted or slowed. Also observe patients for 30 minutes after the infusion is completed for acute infusion reactions. Sipuleucel-T should not be held at room temperature for more than 3 hours. Observe universal precautions when handling sipuleucel-T and leukapheresis material; sipuleucel-T is not routinely tested for transmissable diseases.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Antithymocyte Globulin: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Azathioprine: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Basiliximab: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Cyclosporine: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Dexamethasone: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Methylprednisolone: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Prednisolone: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Prednisone: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
Rituximab: (Moderate) Use rituximab and sipuleucel-T together with caution. If appropriate, consider reducing or discontinuing immunosuppressive agents prior to treatment with sipuleucel-T. Sipuleucel-T works by stimulating the immune system; therefore, concurrent use with immunosuppressive agents, such as rituximab, may alter its efficacy or safety.
Rituximab; Hyaluronidase: (Moderate) Use rituximab and sipuleucel-T together with caution. If appropriate, consider reducing or discontinuing immunosuppressive agents prior to treatment with sipuleucel-T. Sipuleucel-T works by stimulating the immune system; therefore, concurrent use with immunosuppressive agents, such as rituximab, may alter its efficacy or safety.

Provenge Intravenous Inj Susp

Maximum dosage limits not defined. Each dose of sipuleucel-T contains the maximum number of cells that can be manufactured from a single leukapheresis procedure. The number of cells in sipuleucel-T does not exceed the number of cells collected from leukapheresis.

Maximum dosage limits not defined. Each dose of sipuleucel-T contains the maximum number of cells that can be manufactured from a single leukapheresis procedure. The number of cells in sipuleucel-T does not exceed the number of cells collected from leukapheresis.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate T-cell immunity against prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue but not in non-prostate tissue. While the exact mechanism of action is unknown, it is dependent upon the effective presentation of this target antigen to the patient's immune system. The active components of sipuleucel-T are antigen presenting cells (APCs) and PAP-GM-CSF; APCs are responsible for the presentation of antigens to T cells.The APCs within sipuleucel-T are from autologous peripheral blood mononuclear cells, which are obtained during a standard leukapheresis procedure that the patient undergoes approximately 3 days prior to the infusion. The APCs are activated during a culture period with a recombinant human protein, PAP-GM-CSF, which consists of PAP linked to granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune cell activator. During the culture process with PAP-GM-CSF, APCs take up and process the recombinant target antigen into small peptides that are then displayed on the APC surface. Minimal residual levels of the intact PAP-GM-CSF are detectable in the final sipuleucel-T product. The recombinant antigen is designed to target APCs and may help direct the immune response to PAP. The potency of sipuleucel-T is determined in part by measuring the increased expression of the CD54 molecule on the surface of the APCs after culture with PAP-GM-CSF. CD54, also known as ICAM-1, is a cell surface molecule that plays a role in immunologic interactions between APCs and T-cells, and is considered a marker of immune-cell activation. The final cellular composition of sipuleucel-T is dependent upon the cellular composition of the leukapheresis product. In addition to APCs, the final product contains T cells, B cells, natural killer (NK) cells, and other cells.

Sipuleucel-T is administered by intravenous infusion. It is a dendritic cell product that consists of autologous dendritic-cells loaded with prostatic-acid phosphatase linked to granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF). In a phase III controlled clinical trial, 237 patients with prostate cancer were evaluated for the development of humoral and T cell immune responses (proliferative and gamma-interferon ELISPOT) to the target antigens (at baseline and at weeks 6, 14, and 26). IgG and IgM antibody responses against PAP-GM-CSF and against PAP alone were observed through the follow-up period. T cell proliferative and gamma-interferon ELISPOT responses were observed in peripheral blood collected in the follow-up period from patients receiving sipuleucel-T. Responses were not observed in the control group. Some sipuleucel-T patients exhibited a response to PAP antigen alone. The clinical significance of antibody responses is not known. In another trial, the specific T-cell responsiveness against the target antigen was determined in a small group of patients whose cells were processed within 24 hours of collection. The median ratio of the PA2024 (a recombinant fusion protein containing prostatic acid phosphatase and GM-CSF) T-cell stimulation index at 8 weeks versus baseline was approximately eight-fold higher in sipuleucel-T- versus placebo-treated patients.

The FDA has not assigned a pregnancy category for sipuleucel-T. The only indication at the time of FDA approval was for men; sipuleucel-T is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. No studies on the effects of sipuleucel-T on fertility have been conducted.

Information regarding the safety of breast-feeding for a patient taking sipuleucel-T was not available at the time of FDA approval. The only indication at FDA approval was for men; sipuleucel-T is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.