Talimogene laherparepvec (T-VEC)

What is talimogene laherparepvec?

Talimogene laherparepvec (T-VEC) is a medication comprised of a genetically engineered attenuated strain of herpes simplex virus 1 with anti-tumour immune properties, used to treat melanoma.

T-VEC (brand name Imlygic®, previously OncoVEX^GM-CSF) is one of the first globally approved oncolytic immunotherapeutic medications. It was approved by the United States Food and Drug Administration (FDA) and also by the European Medicines Agency (EMA) in 2015.

Multiple cutaneous metastasis from a melanoma, a potential candidate for talimogene 

What is talimogene laherparepvec used for?

Talimogene laherparepvec (T-VEC) is predominantly used to treat unresectable metastatic melanoma in adult patients with no bone, brain, lung, or other visceral metastatic diseases.

Early-stage clinical trials are testing whether T-VEC may also be effective in treating:

• Pancreatic cancer
• Soft-tissue sarcoma
• Head and neck cancer.

How does talimogene laherparepvec work?

Talimogene laherparepvec (T-VEC) is an oncolytic viral immunotherapy derived from Herpes simplex virus 1 (HSV-1).

It has been genetically modified (including deletions of ICP34.5 and ICP47) to selectively replicate within tumours and produce granulocyte-macrophage colony-stimulating factor (GM-CSF), causing tumour cell death and the release of tumour-derived antigens. This promotes an effector T-cell and systemic anti-tumour immune response.

What are the contraindications with talimogene laherparepvec?

• Hypersensitivity to T-VEC or any of its excipients
• Pregnancy
• Breastfeeding
• Herpes simplex infection
• Severe immunodeficiency

Dosing and administration

Talimogene laherparepvec (T-VEC) is given via intralesional injection. Dosing is dependent on lesion size and treatment phase.

2 concentrations:

• Initial treatment: 10⁶ plaque-forming units (PFU)/mL
• Subsequent treatments: 10⁸ PFU/mL.

Dose:

• ≤0.5 cm — use ≤0.1 mL
• >0.5–1.5 cm — use ≤0.5 mL
• >1.5–2.5 cm — use ≤1 mL
• >2.5–5 cm — use ≤2 mL
• >5cm — use ≤4 mL.

Use up to 4mL total across all lesions per visit.

Treatment should be continued for at least 6 months, except if:

• No injectable lesions remain
• Serious/intolerable side effects or new contraindications arise
• Deemed ineffective.

Administration notes

• T-VAC comes in single-use 1 mL vials, colour coordinated by viral concentration, and should be thawed at room temperature prior to use; transportation and handling protocols should be followed.
• During initial treatment, the largest lesion should be injected first, followed by remaining lesions in decreasing size order until up to 4 mL total has been injected.
• Subsequent treatments (2–3-week intervals): begin with any new lesions, then continue based on size order until all lesions are injected (or 4 mL has been used).
• Administer directly into melanoma lesions (cutaneous, subcutaneous, or nodal) that are visible, palpable, or detectable by ultrasound before covering with an occlusive dressing.
• Contact with treated lesions should be avoided to prevent potential viral transmission.
  • Healthcare workers should use personal protective equipment (PPE).
  • Advise patients to regularly wash hands, use condoms during sexual contact, and avoid touching infection site(s) to prevent viral transmission.

What are the benefits of talimogene laherparepvec?

In the OPTiM study, T-VEC showed a higher durable response rate when compared with GM-CSF intralesional injection (16.3% vs 2.1% respectively) and overall response rate (26.4% vs. 5.7% respectively) in patients with stage IIIB, IIIC, and IVM1a melanoma.

T-VEC has also demonstrated potential systemic immune effects, by reducing the size of the following lesions by at least half:

• 64% of injected lesions
• 34% of uninjected non-visceral lesions
• 15% of uninjected visceral lesions.

T-VEC is generally well tolerated and has a good safety profile (see more below).

What are the disadvantages of talimogene laherparepvec?

• Variable onset of effects due to individual treatment response and stage of melanoma.
• Insufficient evidence to clearly prove enhanced overall survival; further research is ongoing.
• While some effect on visceral metastases has been demonstrated, T-VEC is not as effective against visceral lesions as non-visceral lesions.
• Patients may experience increased size of existing lesions or newly emerging lesions before achieving full treatment response.
• Strict requirements for handling and storing.
• Accidental exposure may lead to transmission of T-VEC, potentially causing herpes simplex infection.

What are the side-effects and risks of talimogene laherparepvec?

Common side-effects of T-VEC include:

• Injection-site pain
• Flu-like symptoms (up to 90% within the first 6 months)
• Nausea
• Fever
• Chills
• Fatigue.

Other reported adverse effects include rash, cellulitis (~2%), herpetic infections (including oral herpes), and a number of immune-mediated events such as worsening psoriasis, vasculitis, glomerulonephritis, and vitiligo.

Patients should be advised to seek medical attention if the following symptoms of potential herpes infection develop, such as:

• Pain, burning, or tingling sensation in a blister affecting the mouth, ears, fingers, or genitals
• Eye pain, blurry vision, or ooze/discharge from the eyes
• Sensitivity to bright light (photophobia)
• Upper or lower limb weakness
• Extreme sleepiness/drowsiness
• Mental confusion.

Drug interactions

• No specific drug interaction studies have been undertaken.
• Antivirals (eg, acyclovir/ aciclovir) could potentially interfere with T-VEC efficacy; consider risks and benefits before commencing antivirals for treatment of herpetic infection.

Use in specific populations

• Paediatric — not approved for use as no safety or efficacy data in children.
• Pregnancy — no data but theoretical risk of transmission across placenta (which can occur with wild-type herpes simplex virus) therefore avoidance recommended.
  • Contraceptive counselling should be offered to all patients at risk of pregnancy prior to commencing T-VEC therapy.
  • Pregnant healthcare staff should not administer T-VEC.
• Breastfeeding — no data; transmission unknown; consider risks and benefits.
• Elderly — no dose adjustments required.
• Renal or hepatic impairment — no dose adjustments required.
• Immunocompromised — minimal data, however avoidance recommended due to potential increased risk of disseminated herpetic infection (especially if severely immunocompromised).

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).