Dosing and uses of Imlygic (talimogene laherparepvec)
Adult dosage forms and strengths
solution for intralesional injection
- 10^6 (1 million) plaque-forming units (PFU) per mL (available as 1-mL single-use vial)
- 10^8 (100 million) PFU per mL solution (available as 1-mL single-use vial)
Melanoma
Genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrence after initial surgery
Administer by injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance (see Administration)
Total injection volume
- The total injection volume for each treatment visit should not exceed 4 mL for all injected lesions combined
- It may not be possible to inject all lesions at each treatment visit or over the full course of treatment
- Previously injected and/or uninjected lesion(s) may be injected at subsequent treatment visits
Dose
- Initial dose: Up to 4 mL at a concentration of 10^6 (1 million) PFU per mL
- Second dose: Up to 4 mL at a concentration of 10^8 (100 million) PFU per mL administered 3 weeks after initial treatment
- All subsequent treatments (including reinitiation): Up to 4 mL at a concentration of 10^8 (100 million) PFU per mL administered 2 weeks after previous treatment
- Continue treatment for at least 6 months unless other treatment is required or until there are no injectable lesions to treat
- Reinitiate treatment if new unresectable cutaneous, subcutaneous, or nodal lesions appear after a complete response
Prioritize lesions to be injected
- Initial injection: Inject largest lesion(s) first; prioritize injection of remaining lesion(s) based on lesion size until maximum injection volume is reached or until all injectable lesion(s) have been treated
- Second and all subsequent injections: Inject any new lesion(s) (lesions that have developed since the previous treatment) first; prioritize injection of remaining lesion(s) based on lesion size until maximum injection volume is reached or until all injectable lesion(s) have been treated
Determine dose volume for each lesion
- Lesion sizes are based on the longest dimension
- When lesions are clustered together, inject them as a single lesion according the following:
- >5 cm: Up to 4 mL/lesion
- >2.5 to 5 cm: Up to 2 mL/lesion
- >1.5 to 2.5 cm: Up to 1 mL/lesion
- >0.5 to 1.5 cm: Up to 0.5 mL/lesion
- <0.5 cm: Up to 0.1 mL/lesion
Dosage modifications
Hepatic or renal impairment: No clinical studies have been conducted to evaluate the effect of hepatic or renal impairment on the pharmacokinetics of talimogene laherparepvec
Dosing Considerations
Limitations of use: Has not been shown to improve overall survival or have an effect on visceral metastases
Pediatric dosage forms and strengths
Safety and efficacy not established
Imlygic (talimogene laherparepvec) adverse (side) effects
>10%
Fatigue, all grades (50.3%)
Chills, all grades (48.6%)
Pyrexia, all grades (42.8%)
Nausea, all grades (35.6%)
Influenzalike illness, all grades (30.5%)
Injection site pain, all grades (27.7%)
Vomiting, all grades (21.2%)
Diarrhea, all grades (18.8%)
Headache, all grades (18.8%)
Myalgia, all grades (17.5%)
Arthralgia, all grades (17.1%)
Pain in extremity, all grades (16.4%)
Constipation, all grades (11.6%)
1-10%
Dizziness, all grades (9.6%)
Abdominal pain, all grades (8.9%)
Oropharyngeal pain, all grades (5.8%)
Weight decreased, all grades (5.8%)
Fatigue, grade 3 (2.1%)
Vomiting, grade 3 (1.7%)
Pain in extremity, grade 3 (1.4%)
<1%
Influenzalike illness, grade 3
Injection site pain, grade 3
Nausea, grade 3
Diarrhea, grade 3
Abdominal pain, grade 3
Myalgia, grade 3
Arthralgia, grade 3
Headache, grade 3
Weight decreased, grade 3
Warnings
Contraindications
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 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
Pregnant women
Cautions
Accidental exposure may lead to transmission of herpetic infection; accidental needle stick and splash-back to the eyes have been reported in healthcare providers during preparation and administration; use universal chemotherapy handling precautions
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 (see Contraindications)
Herpetic infections, including cold sores and herpetic keratitis, reported in treated patients; disseminated herpetic infection may also occur in immunocompromised patients (see Contraindications)
Injection site complications, including necrosis or ulceration of tumor tissue, may occur during treatment; cellulitis and systemic bacterial infection have been reported; careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds; consider the risks and benefits before continuing treatment
Treatment may result in immune-mediated events, including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo; consider the risks and benefits before initiating treatment
Plasmacytoma has been reported in proximity to the injection site after administration in a patient with smoldering multiple myeloma; consider risks and benefits in patients with multiple myeloma or in whom plasmacytoma develops during treatmen
Pregnancy
Pregnancy
Contraindicated in pregnancy because of the risk of transmitting wild-type HSV-1 cross the placental barrier and the risk of transmission during birth owing to viral shedding
Female patients of childbearing potential should use an effective method of contraception to prevent pregnancy during treatment
Infections with wild-type HSV-1 have been associated with serious adverse effects, including multiorgan failure and death, if a fetus or neonate contracts the wild-type herpes infection
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
Lactation
Unknown if distributed in human breast milk; because medicinal products can be found in human milk, a decision should be made whether to discontinue nursing or to discontinue the drug while nursing
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Imlygic (talimogene laherparepvec)
Mechanism of action
Exact mechanism of action is unknown
Genetically modified, live, attenuated herpes simplex virus programmed to replicate within tumors and to produce the immune stimulatory protein GM-CSF
Causes lysis of tumors, followed by release of tumor-derived antigens, which together with virally derived GM-CSF may promote an antitumor immune response
Administration
Handling
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
Avoid accidental exposure and follow universal biohazard precautions for preparation, administration, handling, and disposaL
Preparation
Thawing
- Determine total volume required for injection (up to 4 mL)
- Thaw frozen vials at room temperature (20-25ºC [68-77ºF]) until liquid (~30 minutes)
- Do not expose the vial to higher temperatures
- Keep the vial in original carton during thawing
- Swirl gently; do NOT shake
- After thawing, administer immediately or store refrigerated (see Storage)
Prepare syringes
- Prepare sterile syringes and needles
- A detachable needle of 18-26 gauge may be used for withdrawal and a detachable needle of 22-26 gauge may be used for injection
- Small-unit syringes (eg, 0.5-mL insulin syringes) are recommended for better injection control
- Using aseptic technique, remove the vial cap and withdraw the product from the vial into the syringe(s), noting the total volume
- Avoid generating aerosols when loading syringes with product, and use a biologic safety cabinet if available
Intralesional Administration
For intralesional injection only; do not administer IV
Administer by injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance
Preinjection preparation
- Clean the lesion and surrounding areas with an alcohol swab and let dry
- Treat the injection site with a topical or local anesthetic agent, if necessary
- Do not inject anesthetic agent directly into the lesion
- Inject anesthetic agent around the periphery of the lesion
Injection
- Inject intralesionally into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance
- Using a single insertion point, inject solution along multiple tracks as far as the radial reach of the needle allows within the lesion to achieve even and complete dispersion
- Multiple insertion points may be used if a lesion is larger than the radial reach of the needle
- Inject evenly and completely within the lesion by pulling the needle back without exiting the lesion
- Redirect the needle as many times as necessary while injecting the remainder of the dose
- Continue until the full dose is evenly and completely dispersed
- When removing the needle, withdraw it from the lesion slowly to avoid leakage of solution at the insertion point
- Repeat preinjection preparation and the above injection procedure for other lesions to be injected
- Use a new needle any time the needle is completely removed from a lesion and each time a different lesion is injected
Postinjection
- Apply pressure to the injection site(s) with sterile gauze for at least 30 seconds
- Swab the injection site(s) and surrounding area with alcohol
- Change gloves and cover the injected lesion(s) with an absorbent pad and dry occlusive dressing
- Wipe the exterior of occlusive dressing with alcohol
- Advise patients to keep the injection site(s) covered for at least the first week after each treatment visit or longer if the injection site is weeping or oozing
- Instruct patients to replace the dressing if it falls off
- The patient should avoid touching or scratching the injection sites or the occlusive dressing as it may lead to inadvertent transfer of injection solution to other parts of the body
Storage
Store and transport frozen at -90°C to -70°C (-130°F to -94°F)
Protect from light
Store frozen in the carton until use
Thaw immediately prior to administration (see Preparation)
Do not draw thawed solution into a syringe until immediately prior to administration
Thawed vials
- After thawing at room temperature (see Preparation), administer immediately or store in its original vial and carton, protected from light in a refrigerator (2-8°C [36° to 46°F])
- Do not refreeze after thawing
- Discard (according to chemotherapy guidelines) any vial left in the refrigerator longer than the specified times listed below
- 10^6 (1 million) PFU per mL: Do not exceed 12 hr of refrigeration storage
- 10^8 (1 million) PFU per mL: Do not exceed 48 hr of refrigeration storage
