Dr Hamid on the Use of Lifileucel in Advanced Melanoma

Omid Hamid, MD, director, Melanoma Program, Cedars-Sinai Medical Center, chief, Translational Research and Immunotherapy, director, Melanoma Therapeutics, Phase I Immuno-Oncology Program, The Angeles Clinic and Research Institute, discusses the use of lifileucel (Amtagvi) in the treatment of patients with advanced melanoma.

On February 16, 2024, the FDA granted accelerated approval to lifileucel for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor. The regulatory decision was supported by data from the phase 2 C-144-01 trial (NCT02360579), which demonstrated that patients treated with the recommended dose (n = 73) experienced an objective response rate of 31.5% (95% CI, 21.1%-43.4%), including a complete response rate of 4.1% and a partial response rate of 27.4%.

Lifileucel is an adoptive T cell therapy that is engineered using extracted T cells that reside in tumors, which are inherently equipped to recognize multiple antigens within the tumor microenvironment, Hamid explains. The extracted T cells then go through a rapid expansion protocol, creating a sizable population primed for tumor recognition, he continues. Prior to reinfusion, patients with advanced melanoma undergo lymphodepleting chemotherapy to remove other T cells from the tumor microenvironment, Hamid explains, noting that the engineered T cells are then reinfused into patients.

The therapeutic efficacy of lifileucel hinges upon the inherent ability of these reinfused T cells to recognize and target tumor-specific antigens, Hamid continues. By leveraging the natural immune response against malignant cells, lifileucel aims to induce a potent and sustained antitumor immune reaction. To bolster this response, adjunctive administration of interleukin-2 (IL-2) is employed to augment immune activation and propagation.

In essence, the mechanism of action underlying tumor-infiltrating lymphocyte therapy involves a multi-step process, Hamid says. By orchestrating a concerted immune assault on the tumor microenvironment, lifileucel holds promise as a novel therapeutic modality in the management of melanoma. Through its intricate mechanism of action, lifileucel seeks to harness the inherent antitumor potential of T cells and minimize collateral damage to healthy cells, Hamid explained. Looking toward the future, ongoing research endeavors continue to elucidate the nuances of adoptive T-cell therapies, and the integration of lifileucel into the melanoma treatment armamentarium underscores the evolving landscape of precision oncology, Hamid concludes.