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The standard of care for patients with locoregional advanced or metastasized melanoma is to render a patient free of disease as long as the disease is sufficiently limited. When this is no longer feasible, intralesional therapy is a possible option due to its good local response and tolerable adverse-event profile, as well as the option to provide outpatient treatment. A bystander effect observed in various agents adds to its appeal. During the last few decades, other agents have been tested for intralesional therapy with varying success. Many intralesional compounds now available produce a broad range of local response rates. The ideal agent should have a low toxicity profile, be easy to administer, lead to fast responses, and trigger a systemic immune response, thereby creating a bystander effect. These criteria were predominantly met in the results of trials using 10% rose bengal and talimogene laherparepvec in up to 40% of study patients.

Most agents (Bacille-Calmette-Guerin, interferon, granulocyte macrophage colony-stimulating factor) demonstrated inconsistent rates of efficacy, but the treatment field changed when velimogene aliplasmid, 10% rose bengal, and talimogene laherparepvec were introduced. Velimogene aliplasmid did not meet its primary end point in a phase 3 trial, but talimogene laherparepvec did meet its phase 3 trial objectives, demonstrating a survival benefit in select study patients. The results of phase 2 results of 10% rose bengal trials are also promising and a phase 3 is still recruiting (NCT02288897). Other options include combinations of intralesional therapies and systemic therapies, including ipilimumab/talimogene laherparepvec and pembrolizumab/rose bengal (NCT02557321).

Our treatment approach should be individualized per patient, based on the extent of disease, tumor characteristics, and disease-free interval, as well as patient characteristics such as age, performance status, and comorbidities, and work to maintain quality of life for as long as possible. An appropriate approach is often not a single therapy but rather a combination of injectable treatments, regional perfusion therapies, and systemic therapies.


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