Sipuleucel-t (Monograph)

Brand name: Provenge
Drug class: Cellular Therapy

Medically reviewed by Drugs.com on Dec 12, 2023. Written by ASHP.

Introduction

Sipuleucel-t is an autologous cellular immunotherapy.

Uses for Sipuleucel-t

Sipuleucel-t has the following uses:

Sipuleucel-t is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

Treatment with sipuleucel-t requires collection of peripheral blood mononuclear cells from the patient by leukapharesis; the cells are exposed to a medium containing prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue, conjugated to granulocyte-macrophage colony-stimulating factor (GM-CSF). The activated cells are then infused back into the patient.

Efficacy of sipuleucel-t was evaluated in 2 randomized, double-blind, placebo-controlled multicenter trials in men with metastatic castrate-resistant prostate cancer. Patients underwent a series of 3 leukapheresis procedures (at approximately Weeks 0, 2, and 4), followed approximately 3 days later by IV infusion of sipuleucel-t or control (autologous peripheral blood mononuclear cells that had not been activated). In one of the studies, median overall survival was 25.8 months in patients receiving sipuleucel-t compared with 21.7 months in patients receiving control. In the other study, median overall survival was 25.9 months in patients receiving sipuleucel-t compared with 21.4 months in patients receiving control.

Sipuleucel-t Dosage and Administration

General

Sipuleucel-t is available in the following dosage form(s) and strength(s):

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.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

For autologous use only. For IV use only.

• Do not use sipuleucel-t until confirmation of product release is received from the manufacturer (Dendreon).

• The recommended course of therapy is 3 doses given at approximately 2-week intervals. In controlled clinical trials, the median dosing interval between infusions was 2 weeks (range 1 to 15 weeks); the maximum dosing interval has not been established.

• Premedicate patients with oral acetaminophen and an antihistamine such as diphenhydramine approximately 30 minutes prior to administration of sipuleucel-t.

• Before infusion, confirm that the patient's identity matches the patient identifiers on the infusion bag.

• Infuse sipuleucel-t IV over a period of approximately 60 minutes. Do not use a cell filter.

• Observe the patient for acute infusion reactions for at least 30 minutes following each infusion. Interrupt or slow infusion for acute infusion reactions, depending on the severity of the reaction.

• See Full Prescribing Information for additional instructions on preparation and administration.

Related/similar drugs

estradiol, Premarin, Xtandi, Zytiga, Casodex, Lynparza

Cautions for Sipuleucel-t

Contraindications

None.

Warnings/Precautions

Acute Infusion Reactions

Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia.

In controlled clinical trials, 71.2% of patients in the sipuleucel-t group developed an acute infusion reaction. The most common events (≥ 20%) were chills, fever, and fatigue. In 95.1% of patients reporting acute infusion reactions, the reactions were mild or moderate. Fevers and chills generally resolved within 2 days (71.9% and 89%, respectively).

In controlled clinical trials, severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the sipuleucel-t group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. The incidence of severe events was greater following the second infusion (2.1% vs. 0.8% following the first infusion), and decreased to 1.3% following the third infusion. Some (1.2%) patients in the sipuleucel-t group were hospitalized within 1 day of infusion for management of acute infusion reactions. No Grade 4 or 5 acute infusion reactions were reported in patients in the sipuleucel-t group.

Closely monitor patients with cardiac or pulmonary conditions. In the event of an acute infusion reaction, decrease the infusion rate or stop the infusion, depending on the severity of the reaction. Administer appropriate medical treatment as needed.

Thromboembolic Events

Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of sipuleucel-t. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. Sipuleucel-t should be used with caution in patients with risk factors for thromboembolic events.

Vascular Disorders

In controlled clinical trials, cerebrovascular events (hemorrhagic and ischemic strokes) were observed in 3.5% of patients in the sipuleucel-t group compared with 2.6% of patients in the control group. In the postmarketing setting, cerebrovascular events, including transient ischemic attacks, have been observed following infusion of sipuleucel-t. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

In controlled clinical trials, myocardial infarctions were observed in 0.8% of patients in the sipuleucel-t group compared with 0.3% of patients in the control group. In the postmarketing setting, myocardial infarctions have been observed following infusion of sipuleucel-t. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

Handling Precautions for Control of Infectious Disease

Sipuleucel-t is not tested for transmissible infectious diseases. Therefore, patient leukapheresis material and sipuleucel-t may carry the risk of transmitting infectious diseases to health care professionals handling the product. Accordingly, health care professionals should employ universal precautions when handling leukapheresis material or sipuleucel-t.

Concomitant Chemotherapy or Immunosuppressive Therapy

Use of either chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or sipuleucel-t has not been studied. Sipuleucel-t is designed to stimulate the immune system, and concurrent use of immune-suppressive agents may alter the efficacy and/or safety of sipuleucel-t. Therefore, evaluate patients carefully to determine whether it is medically appropriate to reduce or discontinue immunosuppressive agents prior to treatment with sipuleucel-t.

Product Safety Testing

Sipuleucel-t is released for infusion based on the microbial and sterility results from several tests: microbial contamination determination by Gram stain, endotoxin content, and in-process sterility with a 2-day incubation to determine absence of microbial growth. The final (7-day incubation) sterility test results are not available at the time of infusion. If the sterility results become positive for microbial contamination after sipuleucel-t has been approved for infusion, Dendreon will notify the treating physician. Dendreon will attempt to identify the microorganism, perform antibiotic sensitivity testing on recovered microorganisms, and communicate the results to the treating physician. Dendreon may request additional information from the physician in order to determine the source of contamination.

Specific Populations

Geriatric Patients

In controlled clinical trials, 72.9% of patients (438 of 601) in the sipuleucel-t group were ≥ 65 years of age. There were no apparent differences in the safety of sipuleucel-t between patients ≥ 65 years of age and younger patients.

In a survival analysis of the controlled clinical trials of sipuleucel-t in metastatic castrate-resistant prostate cancer, 78.3% of randomized patients (382 of 488) were ≥ 65 years of age. The median survival of patients in the sipuleucel-t group ≥ 65 years of age was 23.4 months (95% confidence interval 22.0, 27.1), compared with 17.3 months in the control group (95% confidence interval: 13.5, 21.5).

Race

In controlled clinical trials, 90.6% of patients were Caucasian, 5.8% were African American, and 3.7% were “Other”. Due to the low numbers of non-Caucasian patients in the trials, no conclusions can be made regarding the safety or efficacy of sipuleucel-t by race.

Common Adverse Effects

The most common adverse reactions (incidence ≥ 15%) are chills, fatigue, fever, back pain, nausea, joint ache, and headache.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Actions

Mechanism of Action

Sipuleucel-t is classified as an autologous cellular immunotherapy. While the precise mechanism of action is unknown, sipuleucel-t is designed to induce an immune response targeted against 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.

In a randomized placebo-controlled study, 237 out of the 512 patients randomized were evaluated for the development of humoral and T cell immune responses (proliferative and gamma-interferon (γIFN) ELISPOT) to the target antigens at Baseline, and at Weeks 6, 14, and 26. Antibody (IgM and IgG) responses against PAP-GM-CSF and PAP antigen alone were observed through the follow-up period in the sipuleucel-t group. Neutralizing antibody responses to GM-CSF were transient. T cell proliferative and γIFN ELISPOT responses to PAP-GM-CSF fusion protein were observed in cells collected from peripheral blood of patients through the follow-up period in the sipuleucel-t treatment group but not in controls. In some patients a response to PAP antigen alone was observed. No conclusions could be made regarding the clinical significance of the observed immune responses.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.

• Advise patients that the recommended course of therapy for sipuleucel-t is 3 complete doses. Each infusion of sipuleucel-t is preceded by a leukapheresis procedure approximately 3 days prior. It is important to maintain all scheduled appointments and arrive at each appointment on time because the leukapheresis and infusions must be appropriately spaced and the sipuleucel-t expiration time must not be exceeded.

• Advise patients that if they are unable to receive an infusion of sipuleucel-t, they will need to undergo an additional leukapheresis procedure if the treatment is to be continued.

• Counsel the patient on the importance of adhering to preparation instructions for the leukapheresis procedure, the possible side effects of leukapheresis, and post-procedure care.

• If the patient does not have adequate peripheral venous access to accommodate the leukapheresis procedure and infusion of sipuleucel-t, inform the patient about the need for a central venous catheter. Counsel the patient on the importance of catheter care. Instruct the patient to tell their doctor if they are experiencing fevers or any swelling or redness around the catheter site, because these symptoms could be signs of an infected catheter.

• Advise patients to report signs and symptoms of acute infusion reactions such as fever, chills, fatigue, breathing problems, dizziness, high blood pressure, low blood pressure, lightheadedness, nausea, vomiting, headache, or muscle aches.

• Advise patients to report any symptoms suggestive of cardiac arrhythmia, cardiac ischemia, cerebral ischemia, deep-vein thrombosis, or pulmonary embolism.

• Advise patients to inform their doctor if they are taking immunosuppressive agents.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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