Talimogene laherparepvec (T-VEC) is an intratumoral oncolytic virotherapy of genetically modified herpes simplex virus type 1 (HSV-1). In 2015, T-VEC was US Food and Drug Administration (FDA)-approved for the treatment of adults with metastatic melanoma, specifically unresectable cutaneous, subcutaneous, or nodal melanoma lesions recurrent after surgery. The drug is injected directly into cutaneous metastases, which causes both direct tumor cell lysis and stimulation of systemic antitumor immunity through upregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF).

Systemic reactions are common and include fever, chills, an influenza-like illness, and fatigue. The most frequent cutaneous event is a localized injection-site reaction, including erythema, pain, and swelling. Five cases of a granulomatous dermatitis developing at intratumoral injection sites have been reported, confounding assessment of tumor response, and ultimately requiring biopsies to confirm this diagnosis. Less commonly, neutrophilic dermatitis, lymphoctic dermatitis, and pseudolymphoma have also been described. In a phase I study of Japanese patients with advanced melanoma, ulceration of the tumor tissue at the injection site was reported in 2 of 18 patients (11%). In the OPTiM phase III trial, secondary bacterial cellulitis of the tumor tissue at the injection site was reported in 6 of 295 patients (2%).

Because T-VEC is a live, attenuated HSV-1-based therapy, herpetic eruptions may develop at or near injection sites or, less commonly, at distant mucocutaneous locations such as the oral or anogenital areas. These herpetic eruptions are uncommon, generally self-limited, and can arise from the therapeutic virus itself or, less commonly, reactivation of latent HSV. T-VEC is contraindicated in patients with active herpetic infection, those requiring daily antiviral therapy, and immunocompromised individuals who are at risk for disseminated herpetic infection.

Vitiligo has been observed in up to 5% of treated melanoma patients. Vitiligo can appear at injection sites or distant skin regions and is often associated with durable antitumor responses. It develops later in the treatment course, often after several months of repeated therapy or even after the final injection, and tends to remain stable and permanent. Postmarketing surveillance has also reported tumoral melanosis after T-VEC therapy. This refers to a melanophage-rich inflammatory infiltrate without viable tumor cells that appears clinically as pigmented lesions, potentially mimicking residual melanoma and complicating response assessment.

When T-VEC is combined with immune checkpoint inhibitors (ICIs), the risk of immune-related cutaneous adverse events from ICIs increases significantly. Large cohort data demonstrate that eczematous dermatitis and lichenoid eruptions occur more frequently in patients receiving ICI plus T-VEC compared to ICI alone. These findings are consistent with mechanistic studies showing that eczematous and lichenoid eruptions represent a spectrum of type 2 immunity-driven cutaneous adverse events in ICI-treated patients. While rare with T-VEC monotherapy, eczematous and lichenoid eruptions should be recognized as potential reactions in the setting of combination therapy.

Overall, the cutaneous side effects of T-VEC are usually manageable with supportive care, wound care, and symptomatic treatment, and they seldom necessitate discontinuation of therapy.