Imlygic

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Imlygic

Classes

Other Antineoplastic Agents

Administration

CAUTION: Observe and exercise universal precautions for handling, preparing, administering, and disposing of biohazardous drugs.
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.
Cover any exposed wounds prior to handling talimogene laherparepvec.
For spills or surfaces that have come into contact with talimogene laherparepvec, clean the area using a virucidal agent such as 1% sodium hypochlorite or 70% isopropyl alcohol; blot using an absorbent material.
Patients should place used dressings and cleaning materials into a sealed plastic bag and dispose in household waste.

Injectable Administration Other Injectable Administration

Intralesional Injection
Preparation:
Determine the total volume needed, up to 4 mL.
Keeping the vial in the original carton, thaw frozen talimogene laherparepvec vials at room temperature (20 to 25 degrees C, or 68 to 77 degrees F) for approximately 30 to 70 minutes (depending on ambient temperature), until talimogene laherparepvec is liquid. Do not expose the vial to higher temperatures.
Swirl gently; do not shake.
Storage after thawing: The 1 million PFU/mL vial is stable for 24 hours when refrigerated at 2 to 8 degrees C (36 to 46 degrees F) and 12 hours when stored at up to 25 degrees C (77 degrees F); the 100 million PFU/mL vial is stable for 7 days when refrigerated and 24 hours when stored at up to 25 degrees C. Protect from light in the original vial and carton. Do not refreeze.
When ready for administration, prepare the syringes and needles. Small unit syringes (e.g., 0.5 mL insulin syringes) are recommended for better injection control. A detachable (18 to 26 gauge) or nondetachable (22 to 26 gauge staked) needle may be used for withdrawal from the vial; a 22 to 26 gauge detachable or nondetachable staked needle may be used for injection.
Administration:
Administer talimogene laherparepvec immediately after preparing syringes.
Clean the lesion and surrounding areas with alcohol; treat the periphery of the lesion with a topical or local anesthetic agent if necessary. Do not inject anesthetic agent directly into the lesion.
Using a single insertion point, inject talimogene laherparepvec along multiple tracks as far as the radial reach of the needle allows within the lesion, to achieve even and complete dispersion; if necessary, pull the needle back without exiting the lesion to allow for redirection as many times as necessary until the full dose is evenly and completely dispersed. Multiple insertion sites may be used if a lesion is larger than the radial reach of the needle.
When removing the needle, withdraw it from the lesion slowly to avoid leakage from the insertion point.
Repeat these steps for all 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.
After injection, apply pressure to the injection site with sterile gauze for at least 30 seconds.
Swab the injection sites and surrounding areas with alcohol.
Change gloves and cover the injected lesions with an absorbent pad and dry occlusive dressing.
Wipe the exterior of the occlusive dressing with alcohol.
Patients should keep the injection site covered for at least the first week after each treatment, or longer if the injection site is still weeping or oozing. Replace the dressing if it falls off.[60260]

Adverse Reactions
Severe

vomiting / Early / 1.7-1.7
injection site reaction / Rapid / 0-1.0
weight loss / Delayed / 0-1.0
abdominal pain / Early / 0-1.0
nausea / Early / 0-1.0
diarrhea / Early / 0-1.0
myalgia / Early / 0-1.0
arthralgia / Delayed / 0-1.0
headache / Early / 0-1.0
glomerulonephritis / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known
pulmonary toxicity / Early / Incidence not known
thrombosis / Delayed / Incidence not known

Moderate

constipation / Delayed / 11.6-11.6
psoriasis / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
impaired wound healing / Delayed / Incidence not known
atopic dermatitis / Delayed / Incidence not known

Mild

dizziness / Early / 9.6-9.6
skin discoloration / Delayed / Incidence not known
rash / Early / Incidence not known

Common Brand Names

Imlygic

Dea Class

Rx

Description

A live, attenuated HSV-1 that has been genetically modified to express human GM-CSF, indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery
Most common adverse drug reactions are fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain
Contraindicated in pregnant women and immunocompromised patients

Dosage And Indications
For the treatment of malignant melanoma.
NOTE: Talimogene laherparepvec has been designated as an orphan drug by the FDA for the treatment of stage IIb to IV melanoma.
For the treatment of unresectable advanced melanoma in patients eligible for local treatment of cutaneous, subcutaneous, and nodal lesions, in combination with ipilimumab†. Intralesional dosage Adults

Dosage not established. Although the overall response rate was improved with talimogene laherparepvec plus ipilimumab compared with ipilimumab alone in a randomized clinical trial; there is not sufficient evidence to support the use of this drug combination for this indication. Talimogene laherparepvec administered up to a dose volume of 4 mL at a concentration of 1 million plaque-forming units (PFU)/mL intralesionally on day 1 of week 1 followed by up to 4 mL at a concentration of 100 million PFU/mL on day 1 of week 4 and then every 2 weeks until complete response, all injectable tumors have disappeared, confirmed disease progression per modified immune-related response criteria, or intolerance was evaluated in a randomized, phase 2 trial (n = 198). In this trial, talimogene laherparepvec was used in combination with ipilimumab 3 mg/kg IV every 3 weeks beginning on day 1 of week 6 for up to 4 infusions.[63055]

For the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that recurred after initial surgery. Intralesional dosage Adults

Dose volume depends on lesion size (measured at the longest dimension) as follows: larger than 5 cm = up to 4 mL; 2.51 to 5 cm = up to 2 mL; 1.51 to 2.5 cm = up to 1 mL; 0.51 to 1.5 cm = up to 0.5 mL; up to 0.5 cm or smaller = up to 0.1 mL. The maximum volume per treatment visit is 4 mL for all lesions combined. If lesions are clustered together, inject them as a single lesion. For the initial intralesional injection, administer the appropriate dose volume for the lesion size at a concentration of 1 million plaque-forming units (PFU)/mL. Inject the largest lesion first; prioritize the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume per treatment has been reached. Starting 3 weeks later, administer the appropriate dose volume for the lesion size at a concentration of 100 million PFU/mL every 2 weeks for at least 6 months unless other treatment is required or until there are no injectable lesions to treat. Inject any new lesions first; prioritize the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume per treatment has been reached. If new unresectable cutaneous, subcutaneous, or nodal lesions develop after a complete response, reinitiate dosing at a concentration of 100 million PFU/mL every 2 weeks.[60260] The durable response rate, defined as complete response plus partial response rate lasting at least 6 months continuously and beginning within the first 12 months of therapy, was significantly higher in patients with unresectable stage IIIB to IV melanoma who received intralesional talimogene laherparepvec compared with subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF) (16.3% vs. 2.1%; p less than 0.001) in a multinational, randomized (2:1), phase III trial (n = 436; the OPTiM trial). Eligible patients (age range, 22 to 94 years) were able to have direct or ultrasound-guided injection into a cutaneous, subcutaneous, or nodal lesion or aggregation of lesions greater than 10 millimeters in diameter. At a median follow-up time of 44.4 months, the median overall survival time was 23.3 months in the talimogene laherparepvec arm and 18.9 months in the GM-CSF arm (hazard ratio = 0.79; 95% CI, 0.62 to 1).[63056]

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available as clinical studies have not been conducted; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available as clinical studies have not been conducted; it appears that no dosage adjustments are needed.

Drug Interactions

Acyclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Amantadine: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Antivirals: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Atazanavir; Cobicistat: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cidofovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Cobicistat: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Darunavir; Cobicistat: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Famciclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Foscarnet: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Ganciclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Ribavirin: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Rimantadine: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valacyclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Valganciclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.

How Supplied

Imlygic Intralesional Inj Susp: 1mL, 1000000pfu, 100000000pfu

Maximum Dosage
Adults

4 mL per treatment visit (all lesions combined).

Geriatric

4 mL per treatment visit (all lesions combined).

Adolescents

Safety and efficacy have not been established in pediatric patients.

Children

Safety and efficacy have not been established in pediatric patients.

Infants

Safety and efficacy have not been established in pediatric patients.

Neonates

Neonates should not be exposed to talimogene laherparepvec due to the risk of transmission of HSV-1. Neonates should avoid direct contact with injected lesions, dressings, or body fluids of treated patients.

Mechanism Of Action

Talimogene laherparepvec is a live, attenuated HSV-1 that has been genetically modified to replicate within tumors and express the immune stimulatory protein, GM-CSF. Administration of a 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. The exact mechanism of action is unknown.

Pharmacokinetics

Talimogene laherparepvec is administered intralesionally.

Other Route(s)

Intralesional Injection Route
In 60 patients with melanoma, talimogene laherparepvec DNA was present in all tested sites following intralesional therapy administered at the recommended dosage: injection-site, n = 60 (100%); blood, n = 59 (98%), occlusive dressing, n = 48 (80%), urine, n = 19 (32%), and oral mucosa, n = 8 (13%). Additionally, 5 of 26 patients (19%) and 3 of 19 patients (16%) had talimogene laherparepvec DNA detected at the anogenital area and at a suspected herpetic lesion sample, respectively. There was no detectable talimogene laherparepvec DNA in blood, urine, oral mucosa, or the anogenital area at 30 days after the end of therapy and in injected lesions at 60 days after the end of therapy. Infectious talimogene laherparepvec virus was detected at the injection site in 7 patients (11%) at multiple time points during the study; however, no samples were positive for viral infectivity after cycle 2 or after the end of treatment.

Pregnancy And Lactation
Pregnancy

Talimogene laherparepvec is contraindicated for receipt during pregnancy; additionally, pregnant women not receiving treatment should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. Healthcare providers who are pregnant should not administer talimogene laherparepvec. If a patient becomes pregnant during treatment, they should be apprised of the potential hazards to the fetus and neonate. If a pregnant woman has an infection with wild-type herpes simplex virus Type 1 (HSV-1), either 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. HSV-1 infections 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 adequate and well-controlled studies conducted in pregnant women, there could be a risk to the fetus or neonate if talimogene laherparepvec acts in the same manner. No effects on embryo-fetal development have been observed in pregnant mice. However, the design of the study limits its application to humans, including administration of talimogene laherparepvec expressing human GM-CSF, which is not biologically active in mice; unknown transplacental kinetics of talimogene laherparepvec in mice; and unknown significance of talimogene laherparepvec dose extrapolation from animal to human based on body weight.

It is not known whether talimogene laherparepvec is present in human milk. Many drugs are excreted in human milk including antibodies. Due to the potential for serious adverse reactions in nursing infants from talimogene laherparepvec, advise women to discontinue breast-feeding during treatment.