Dr Olson on the FDA Approval of Lifileucel for Advanced Melanoma

Daniel Olson, MD, assistant professor, medicine, the University of Chicago Medical Center, discusses the FDA approval of lifileucel (Amtagvi), the first cellular and tumor infiltrating lymphocyte (TIL) therapy product to be approved by the FDA for patients with unresectable or metastatic melanoma whose disease has been previously treated with a PD-1 inhibitor, as well as a BRAF inhibitor with or without a MEK inhibitor for BRAF V600–mutated disease.

This agent was approved on February 16, 2024, based on data from cohorts 2 and 4 of the phase 2 C-144-01 trial (NCT02360579). These data showed that in patients who were treated with the recommended dose of lifileucel (n = 73), the objective response rate was 31.5% (95% CI, 21.1%-43.4%); this included a complete response rate of 4.1% and a partial response rate of 27.4%.

Lifileucel stands out as the first TIL therapy to gain FDA approval, and has a distinct mechanism of action compared with those of other treatments, Olson begins. Unlike typical immunotherapies, lifileucel harnesses the patients’ own T cells extracted from tumors, which are then processed, expanded, and activated externally, he states. Some tumor-derived T cells are anticipated to exhibit reactivity toward the tumor, Olson explains. Curiously, the specific targets within the tumor remain unidentified; however, the T-cell selection process based on tumor proximity enhances the likelihood of obtaining reactive T cells. Upon expansion and reintroduction into the patient, these T cells may target the tumor, he adds.

The lifileucel manufacturing process spans several weeks, during which T cells are isolated, expanded, and activated, Olson continues. Following conditioning chemotherapy, the patient's activated T cells are reintroduced and further activated in vivo with interleukin 2. Ideally, certain subsets of these cells will confront the tumor, migrating back to the disease site and overcoming resistance, he states. Although the precise mechanisms by which these T cells operate to overcome immunotherapy resistance are not fully understood, clinical evidence indicates that even patients unresponsive to previous immunotherapies can derive substantial and enduring benefits from lifileucel, he concludes.