Indication and Use:

• FDA Approved Indication: Talimogene laherparepvec is indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

• Mechanism of Action: T-VEC is a genetically modified oncolytic viral therapy derived from herpes simplex virus type 1 (HSV-1). It works by selectively replicating within tumors and producing granulocyte-macrophage colony-stimulating factor (GM-CSF), which helps kickstart an immune response against the tumor.

Administration and Handling:

• T-VEC is administered via intralesional injection directly into cutaneous, subcutaneous, or nodal lesions.

• T-VEC requires special cold chain storage and handling. Store frozen in an ultra-low temperature freezer or in the original shipping container for up to 96 hours.

• Thaw immediately before administration. Do not re-freeze thawed vials.

Dosing:

• Dosing involves an initial intralesional injection, followed by a second dose three weeks later, and subsequent doses every two weeks.

• Initial dose is up to 4 mL of 10^6 PFU/mL.

• Subsequent doses (given 3 weeks after initial dose, then every 2 weeks) are up to 4 mL of 10^8 PFU/mL.

• The volume of T-VEC injected depends on the size of the lesion. Make sure to follow the recommended dosing volumes and schedules closely.

• Continue treatment for at least 6 months unless other treatment is required or all injectable lesions have resolved.

Adverse Effects:

• Common side effects include fatigue, chills, pyrexia (fever), nausea, flu-like symptoms, and injection site reactions.

• Monitor for signs of immune-related adverse reactions, as T-VEC may potentiate autoimmune responses.

• Educate patients about the possibility of herpetic infections and prescribe prophylactic antiviral therapy if they are immunocompromised.

Managing Adverse Effects:

• Supportive care for flu-like symptoms, including antipyretics and antiemetics, may be prescribed.

• Encourage patients to report any worsening of side effects or new symptoms promptly.

• Be vigilant for herpetic infections and manage them with appropriate antiviral treatments as necessary.

Preparation and Handling:

• T-VEC must be prepared in a biosafety cabinet due to its viral nature. Utilize personal protective equipment (PPE) when handling the drug to avoid exposure.

• Injection Technique:
• Ensure proper intralesional injection technique to ensure adequate delivery of the drug to the tumor.
• Rotate injection sites to prevent overuse of a single lesion.
• Handle needles and syringes with care and dispose of them properly in biohazard containers.

Monitoring and Follow-Up:

• Assess for herpetic infections, especially in immunocompromised patients.

• Monitor injection sites for signs of cellulitis or other complications.

• Evaluate overall tumor response, as some lesions may increase in size before responding to treatment.

• Monitor and document patient's response to therapy, including any reduction in the size of the lesions and systemic symptoms.

• Encourage patients to keep a symptom diary to track any side effects and report these during their follow-up appointments.

Patient Education:

• Advise patients on potential side effects, such as flu-like symptoms and local injection site reactions, and how to manage them.

• Most common side effects include fatigue, chills, fever, nausea, flu-like symptoms, and injection site pain.

• Advise patients to keep injection sites covered for at least 8 days post-treatment.

• Explain to patients the nature of T-VEC as an oncolytic virus and how it works to stimulate an immune response against their melanoma.

• Stress the importance of hygiene and caution to prevent the spread of the live virus, especially around immunocompromised individuals or those who have not had HSV-1 exposure.

• Inform patients about potential for viral shedding and importance of avoiding close contact with immunocompromised individuals.

• Inform patients about the dosing schedule and the importance of adhering to it.

Precautions:

• Contraindicated in immunocompromised patients due to risk of life-threatening disseminated herpetic infection.

• Do not administer to pregnant patients.

• Healthcare providers should wear protective equipment (gown, gloves, eye protection) when preparing or administering T-VEC.

Efficacy Considerations:

• T-VEC has shown particular benefit in patients with earlier stage metastatic disease (Stage IIIB-IVM1a) and those who haven't received prior systemic treatment.

• Consider T-VEC for patients with accessible lesions who have failed other treatment regimens.