Talimogene Laherparepvec (Monograph)
Brand name: Imlygic
Drug class: Gene Therapy
Talimogene laherparepvec, a live attenuated herpes simplex virus type 1 (HSV-1) that has been genetically modified to express human granulocyte macrophage colony-stimulating factor (GM-CSF), is an oncolytic viral therapy.
Uses for Talimogene Laherparepvec
Talimogene laherparepvec has the following uses:
Talimogene laherparepvec is indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Talimogene laherparepvec has been designated an orphan drug by FDA for the treatment of stage IIB to stage IV melanoma.
Talimogene laherparepvec is an oncolytic immunotherapy that selectively replicates within tumors and produces granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance the systemic antitumor immune response. Injections of talimogene laherparepvec into unresectable cutaneous, subcutaneous, and nodal melanoma lesions have been shown to be only modestly effective.
Efficacy and safety of talimogene laherparepvec were evaluated in a multicenter, open-label randomized study that compared intralesional injections of the gene therapy with subcutaneous GM-CSF in patients with melanoma (stage IIIB, IIIC, or IV) that was not surgically resectable. The primary end point was durable response rate (objective response lasting continuously for at least 6 months). Among 436 patients randomized in the study, durable response rate was 16.3% in patients receiving talimogene laherparepvec compared with 2.1% in those receiving GM-CSF. Median time to response was 4.1 months for patients treated with talimogene laherparepvec.
Talimogene laherparepvec has not been shown to improve overall survival or have an effect on visceral metastases; no significant difference in overall survival was observed between the 2 treatment groups in the principal efficacy study.
Talimogene Laherparepvec Dosage and Administration
Talimogene laherparepvec is available in the following dosage form(s) and strength(s):
Single-use vials of 1 mL each in two different dose strengths as follows:
106 (1 million) plaque-forming units (PFU) per mL (light green cap) – for initial dose only
108 (100 million) PFU per mL (royal blue cap) – for all subsequent doses
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
For intralesional injection only. Do not administer IV.
Administer talimogene laherparepvec by injection into cutaneous, subcutaneous, and/or nodal lesions.
Observe special administration procedures and safety precautions when preparing, administering, and handling talimogene laherparepvec.
Healthcare providers who are immunocompromised or pregnant should not prepare or administer talimogene laherparepvec and should not come into direct contact with the injection sites, dressings, or body fluids of treated patients.
The recommended starting dose is up to a maximum of 4 mL of talimogene laherparepvec at a concentration of 106 (1 million) plaque-forming units (PFU) per mL. The recommended dose for subsequent administrations is up to 4 mL of talimogene laherparepvec at a concentration of 108 (100 million) PFU per mL. See Full Prescribing Information for the manufacturer's recommended dosing schedule.
Continue treatment for at least 6 months unless other treatment is required or until there are no injectable lesions to treat.
See Full Prescribing Information for additional instructions on preparation and administration.
Cautions for Talimogene Laherparepvec
Immunocompromised patients. Talimogene laherparepvec is a live, attenuated herpes simplex virus and may cause life-threatening disseminated herpetic infection in patients who are immunocompromised. Do not administer talimogene laherparepvec to immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy.
Accidental Exposure to Talimogene Laherparepvec
Accidental exposure may lead to transmission of talimogene laherparepvec and herpetic infection. Accidental needle stick and splashback to the eyes have been reported in healthcare providers during preparation and administration of talimogene laherparepvec.
Healthcare providers, close contacts (household members, caregivers, sex partners, or persons sharing the same bed), pregnant women, and newborns should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. Healthcare providers who are immunocompromised or pregnant should not prepare or administer talimogene laherparepvec. Caregivers should wear protective gloves when assisting patients in applying or changing occlusive dressings and observe safety precautions for disposal of used dressings, gloves, and cleaning materials.
In the event of an accidental exposure to talimogene laherparepvec, exposed individuals should clean the affected area thoroughly with soap and water and/or a disinfectant. If signs or symptoms of herpetic infection develop, the exposed individuals should contact their healthcare provider for appropriate treatment. Patients should avoid touching or scratching injection sites or their occlusive dressings, as doing so could lead to inadvertent transfer of talimogene laherparepvec to other areas of the body.
Herpetic infections (including but not limited to cold sores and herpetic keratitis) and serious cases of disseminated herpetic infections have been reported in patients treated with talimogene laherparepvec, including fatal disseminated herpetic infection in the immunocompromised patient population. Immunocompromised patients may be at increased risk of life threatening disseminated herpetic infection.
Patients who develop suspicious herpes-like lesions should follow standard hygienic practices to prevent viral transmission. Patients or close contacts with suspected herpetic infections should also contact their healthcare provider to evaluate the lesions. Suspected herpetic lesions should be reported to Amgen at 1-855-IMLYGIC (1- 855-465-9442); patients or close contacts have the option of follow-up testing for further characterization of the infection.
Talimogene laherparepvec is sensitive to acyclovir. Acyclovir or other antiviral agents may interfere with the effectiveness of talimogene laherparepvec. Therefore, consider the risks and benefits of talimogene laherparepvec treatment before administering antiviral agents to manage herpetic infection.
Injection Site Complications
Necrosis or ulceration of tumor tissue may occur during talimogene laherparepvec treatment. Cellulitis and systemic bacterial infection have been reported in clinical studies. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds.
In clinical studies, impaired healing at the injection site has been reported. Talimogene laherparepvec may increase the risk of impaired healing in patients with underlying risk factors (e.g., previous radiation at the injection site or lesions in poorly vascularized areas). One patient had an amputation of a lower extremity 6 months after talimogene laherparepvec injection due to an infected non-healing wound. This wound area had been treated with surgery and radiation prior to talimogene laherparepvec treatment and had previous wound complications.
If there is persistent infection or delayed healing of the injection site(s), consider the risks and benefits of talimogene laherparepvec before continuing treatment.
Talimogene laherparepvec may result in immune-mediated events. In clinical studies, immune-mediated events, including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with talimogene laherparepvec.
Consider the risks and benefits of talimogene laherparepvec before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events.
Plasmacytoma at the Injection Site
In a clinical study, a plasmacytoma has been reported in proximity to the injection site after administration of talimogene laherparepvec in a patient with smoldering multiple myeloma.
Consider the risks and benefits of talimogene laherparepvec in patients with multiple myeloma or in whom plasmacytoma develops during treatment.
Obstructive Airway Disorder
Obstructive airway disorder has been reported following talimogene laherparepvec treatment. Use caution when injecting lesions close to major airways.
Hepatic Hemorrhage from Transcutaneous Intrahepatic Route of Administration
Talimogene laherparepvec is not indicated for transcutaneous intrahepatic route of administration. In clinical studies, cases of hepatic hemorrhage resulting in hospitalization and death have been reported in patients receiving transcutaneous intrahepatic talimogene laherparepvec injections.
Adequate and well-controlled studies with talimogene laherparepvec have not been conducted in pregnant women. No effects on embryo-fetal development have been observed in a study conducted in pregnant mice. The design of the study limits application of the animal data to humans.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
If a patient becomes pregnant while taking talimogene laherparepvec, the patient should be apprised of the potential hazards to the fetus and neonate. Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment with talimogene laherparepvec.
If a pregnant woman has an infection with wild-type Herpes Simplex Virus Type 1 (HSV- 1) (primary or reactivation), there is potential for the virus to cross the placental barrier and also a risk of transmission during birth due to viral shedding. Infections with wild-type HSV-1 have been associated with serious adverse effects, including multi-organ failure and death, if a fetus or neonate contracts the wild-type herpes infection. While there are no clinical data to date on talimogene laherparepvec infections in pregnant women, there could be a risk to the fetus or neonate if talimogene laherparepvec were to act in the same manner.
There is no information regarding the presence of talimogene laherparepvec in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for talimogene laherparepvec and any potential adverse effects on the breastfed infant from talimogene laherparepvec or from the underlying maternal condition.
Because medicinal products can be found in human milk, a decision should be made whether to discontinue nursing or to discontinue talimogene laherparepvec while nursing.
Females and Males of Reproductive Potential
No nonclinical or clinical studies were performed to evaluate the effect of talimogene laherparepvec on fertility.
Safety and effectiveness of talimogene laherparepvec have not been established in pediatric patients.
In clinical studies, no overall differences in safety or efficacy were observed between geriatric patients ( 65 years of age) and younger patients.
No clinical studies have been conducted to evaluate the effect of renal impairment on the pharmacokinetics of talimogene laherparepvec.
No clinical studies have been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of talimogene laherparepvec.
Common Adverse Effects
The most commonly reported adverse drug reactions ( 25%) in talimogene laherparepvec-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain.
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:
Talimogene laherparepvec is sensitive to acyclovir. Acyclovir or other antiherpetic viral agents may interfere with the effectiveness of talimogene laherparepvec.
No drug interaction studies have been conducted with talimogene laherparepvec.
Mechanism of Action
Talimogene laherparepvec has been genetically modified to replicate within tumors and to produce the immune stimulatory protein GM-CSF. Talimogene laherparepvec causes lysis of tumors, followed by release of tumor-derived antigens, which together with virally derived GM-CSF may promote an antitumor immune response. However, the exact mechanism of action is unknown.
Advice to Patients
Advise patients to read the FDA-approved patient labeling (Medication Guide).
Advise patients to follow these instructions to prevent viral transmission: avoid direct contact with injection sites, dressings, or body fluids of patients; wear gloves when changing dressing; avoid touching or scratching injection sites; keep injection sites covered for at least the first week after each treatment visit or longer if the injection site is weeping or oozing and replace dressing if it falls off; dispose of used dressings and cleaning materials in household waste in a sealed plastic bag.
Advise female patients of childbearing potential to use an effective method of contraception to prevent pregnancy during treatment with talimogene laherparepvec.
Advise patients that close contacts who are pregnant or immunocompromised should not change dressings or clean injection sites.
In case of accidental exposure to talimogene laherparepvec, advise patients to clean the exposed area with soap and water and/or a disinfectant. Patients or close contacts with suspected herpetic infections should contact their healthcare provider to evaluate the lesions. Suspected herpetic lesions should be reported to Amgen at 1-855-IMLYGIC (1-855-465-9442); patients or close contacts have the option of follow-up testing for further characterization of the infection.
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.
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.
Suspension, for intralesional injection
106 (1 million) plaque-forming units (PFU) per mL
Imlygic (supplied as a sterile frozen suspension in single-use vials with light green cap)
108 (100 million) PFU per mL
Imlygic (supplied as a sterile frozen suspension in single-use vials with royal blue cap)
AHFS DI Essentials™. © Copyright 2023, Selected Revisions October 27, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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