FDA Approves First Cellular Therapy for Advanced Melanoma

In a landmark decision hailed as a significant advance in the treatment of solid tumor cancers, the Food and Drug Administration has granted accelerated approval to lifileucel, marketed as Amtagvi, a novel cellular therapy for patients battling advanced melanoma. Announced on February 16, the approval marks two major milestones: it is the first approved therapy to harness the body's own immune cells known as Tumor-Infiltrating Lymphocytes (TILs), and it is the first cellular therapy of its kind greenlighted for a solid tumor rather than a blood cancer.

The treatment is specifically indicated for patients with advanced melanoma that has progressed following prior therapy, including certain immune checkpoint inhibitors or targeted drugs. Like the established CAR T-cell therapies, this treatment is highly personalized, manufactured using a patient’s own immune cells. The crucial difference, however, lies in where these cells are sourced. While CAR T-cells are drawn from the circulating blood, the T-cells used for lifileucel are collected directly from the patient’s excised tumor tissue. These TILs, having already migrated to the cancerous site, demonstrate an inherent ability to recognize the tumor.

Once extracted, these natural cancer fighters are not genetically altered. Instead, they are expanded in a laboratory setting to number in the billions, thereby creating a powerful, targeted army. This high-volume population of cells is then delivered back to the patient in a single infusion. To enhance the potency and efficacy of the infused TILs, the complete regimen requires two preparatory steps: a few rounds of high-dose, lymphodepleting chemotherapy administered before the infusion, and several doses of the drug Interleukin-2 (IL-2) given shortly thereafter.

The accelerated approval was grounded in data from a clinical trial involving patients whose cancer had continued to worsen despite previous treatments. Among the participants treated with the approved dose of lifileucel, nearly one-third experienced a measurable reduction in their tumor size. Importantly, a small number of participants saw their tumors disappear completely. Furthermore, of those who responded to the treatment, approximately 40 percent maintained a stable response without cancer progression for at least one year following the single infusion. These results suggest a notable durability, with the longest reported continuous response approaching five years.

While the therapy carries a complex treatment regimen, researchers noted that its side effect profile, while universal among trial participants, appeared different from those associated with CAR T-cell therapy. The most common adverse events—such as anemia, fevers, and drops in certain blood counts—were primarily linked to the necessary preparatory chemotherapy and the post-infusion IL-2. Notably, the study did not report the serious immune-related side effects, such as cytokine release syndrome, that are often seen with other cellular treatments.

Experts view the clearance of lifileucel for advanced melanoma as an essential validation of the TIL therapy approach, a concept pioneered by researchers at the National Cancer Institute more than three decades ago. Though the required pre-infusion chemotherapy and high patient health status currently limit the pool of eligible recipients, researchers express significant optimism. The approval is anticipated to be merely the beginning for this therapeutic strategy, with trials already well underway investigating lifileucel’s potential against other solid tumors, including advanced lung, ovarian, and head and neck cancers. Researchers are now focused on refining the process, seeking to create even more potent TILs and potentially broadening the treatment's applicability to a wider range of patients in the years ahead.

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Source:https://www.cancer.gov/news-events/cancer-currents-blog/2024/fda-amtagvi-til-therapy-melanoma