A number of different oncolytic immunotherapies are in development for advanced melanoma, one of which is talimogene laherparepvec, a genetically modified recombinant herpes simplex virus type 1 (HSV-1). It was approved by the U.S. Food and Drug Administration (FDA) in 2015 and has been shown to significantly improve durable response rate (DRR), offering new hope for a disease that had few new treatment options for several decades.
In their article in the March 2016 issue of the Oncology Nursing Forum, Hoffner, Iodice, and Gasal provided an overview of talimogene laherparepvec for advanced melanoma, including mechanism of action, administration, handling, and other nursing considerations.
Talimogene Laherparepvec for Advanced Melanoma
The only oncolytic immunotherapy for advanced melanoma to be evaluated in a phase III, randomized controlled trial to date, talimogene laherparepvec is FDA-approved for the local treatment of unresectable, cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrence after initial surgery. Although studies have shown significant improvement in DRR, the drug has not been shown to improve overall survival or have an effect on visceral metastases, Hoffner et al. reported.
Talimogene laherparepvec uses HSV-1, the virus that causes fever blisters or cold sores, which can be genetically modified to selectively destroy tumor cells while sparing healthy tissues. According to Hoffner et al., preclinical studies have shown that genetically modified HSV-1 had antitumor activity in mice models, and later studies showed that other genetic modifications could be made to enhance antitumor potency, drive host immune antitumor responses, and reduce clinical risk.
In advanced melanoma, talimogene laherparepvec has a twofold mechanism of action, Hoffner et al. described. First, the virus has a direct oncolytic effect in injected lesions by replicating in tumor cells, resulting in oncolysis and the release of tumor-derived antigens. Second, it produces systemic antitumor immune response, which is enhanced by production of virally derived human GM-CSF.
Nursing Considerations for Talimogene Laherparepvec
Administration: According to Hoffner et al., the drug can be injected in the ambulatory or outpatient setting using universal biohazard precautions. It’s administered as a series of intralesional injections using two concentrations: an initial dose of 106 plaque-forming units per milliliter (PFU/ml) to seroconvert HSV-seronegative patients, and subsequent doses of 108 PFU/ml.
Appropriately trained and qualified healthcare professionals, including nurses, can administer the drug. A gown, safety glasses, and gloves should be worn during preparation and administration. Talimogene laherparepvec is injected intralesionally into cutaneous, subcutaneous, or nodal tumors that are palpable or detectable by ultrasound guidance. Topical or local anesthetics may be used, but these should not be injected directly into the lesions because they may alter the pH of the microenvironment and may impact talimogene laherparepvec’s effectiveness.
No previous trials have studied talimogene laherparepvec injection into visceral lesions (e.g., liver), but clinical studies are currently underway investigating this use.
Hoffner et al. explained that the drug is injected evenly into each lesion using multiple tracks with a single insertion point, unless the tumor is larger than the needle’s radial reach, at which point additional insertion points may be used. (For more specifics about injecting the drug, refer to the full article by Hoffner et al.) The needle should be changed for each new lesion to prevent bacterial infection. After injection, apply pressure with sterile gauze for at least 30 seconds, then cover with occlusive dressing.
Patients should be instructed to keep the injection sites covered for at least the first week after treatment, longer if the site is weeping or oozing, and to replace the dressing if it falls off. They should be told to seal used dressings and cleaning materials in a plastic bag before disposing. Anyone who accessing the injection sites should wash their hands before and after touching it.
Storage: Unopened vials of talimogene laherparepvec must be securely stored and transported at –90°C to –70°C (–130°F to –94°F). They must not be exposed to warmer temperatures unless ready to use because the virus will begin to thaw after 60 seconds. To use, thaw at room temperature until liquid (about 30 minutes). Administer immediately or store in the original vial and carton, protected from light, in a refrigerator for no longer than 12 hours for the 106 PFU/ml vial and 48 hours for the 108 PFU/ml vial.
Because talimogene laherparepvec must be thawed immediately before use and cannot be prepared in advance, Hoffner et al. noted that nurses will have a key role to play in coordinating timing patient appointments with pharmacy. They advised that nurse administration of the drug would allow for the most flexibility and patient convenience.
Secondary transmission: Studies and reports have not demonstrated secondary transmission of talimogene laherparepvec to household contacts, but a theoretical possibility exists because the drug is a live virus. Family members, caregivers, and healthcare providers who have open skin lesions or who are immunocompromised or immunosuppressed are at greatest risk, Hoffner et al. reported. Healthcare providers should always wear proper protective equipment when handling the virus and changing dressing, and those who are pregnant or immunocompromised/immunosuppressed should not administer it or come into contact with treated patients’ injection sites or bodily fluids.
If a spill occurs, treat the area with a virucidal agent (e.g., ethanol or bleach) and dispose any materials according to institution procedures. If a person is exposed through the eyes, mucus membranes, open skin break, or needle stick, clean the area and monitor the person for any signs of infection. Systemic treatment with antiviral therapies may be considered.
For more information about talimogene laherparepvec for advanced melanoma, including more details on clinical studies of the drug and more specific administration information, refer to the full article by Hoffner et al.
Five-Minute In-Service is a monthly feature that offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing or Oncology Nursing Forum (ONF). This edition summarizes “Administration and Handling of Talimogene Laherparepvec: An Intralesional Oncolytic Immunotherapy for Melanoma,” by Mary Elizabeth Davis, RN, MSN, AOCNS®, which was featured in the March 2016 issue of ONF. Questions regarding the information presented in this Five-Minute In-Service should be directed to the ONF editor at ONFEditor@ons.org. Photocopying of this article for educational purposes and group discussion is permitted.