On February 16, 2024, lifileucel (Amtagvi), a tumor-derived autologous T-cell immunotherapy, was granted accelerated approval for adults with unresectable or metastatic melanoma previously treated with a PD-1–blocking antibody, and if BRAF V600 mutation–positive, a BRAF inhibitor with or without a MEK inhibitor.¹ Lifileucel is the first treatment for cancer that uses tumor-infiltrating lymphocytes, or TILs.

Supporting Efficacy Data

Approval was based on the LN-144 trial (ClinicalTrials.gov identifier NCT02360579), in which 73 evaluable patients received a single intravenous infusion of lifileucel at a median dose of 21.1 × 10⁹ viable cells after lymphodepletion with cyclophosphamide, mesna, and fludarabine. After the lifileucel dose, patients received interleukin-2 (aldesleukin) doses to support cell expansion in vivo.

An objective response was observed in 23 of 73 patients (31.5%, 95% confidence interval [CI] = 21.1%–43.4%), with a complete response in 3 (4.1%). A median duration of response was not reached (95% CI = 4.1 months to not reached), with 10 responses ongoing at ≥ 12 months.

How It Is Used

The recommended lifileucel dose is 7.5 × 10⁹ to 72 × 10⁹ viable cells. ­Lifileucel must be administered in an inpatient hospital setting under the supervision of a physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. Product labeling provides instructions on the lymphodepletion regimen, premedication, and a post–lifileucel infusion regimen of aldesleukin.

Safety Profile

Safety data are from 156 adults with unresectable or metastatic melanoma who received a single infusion of lifileucel. The most common adverse events of any grade were chills (76%), nausea (69%), pyrexia (61%), fatigue (56%), tachycardia (47%), diarrhea (47%), febrile neutropenia (47%), vomiting (44%), edema (42%), rash (37%), hypotension (37%), and alopecia (31%). The most common grade ≥ 3 adverse events included febrile neutropenia (47%), hypoxia (12%), infection-pathogen unspecified (11%), pyrexia (10%), and rash (10%). The most common grade 3 or 4 laboratory abnormalities were cytopenias, including thrombocytopenia (78%) and neutropenia (69%); grade 3 or 4 hypophosphatemia occurred in 26%.

Serious adverse events leading to death consisted of severe infections including sepsis and septic shock, pneumonia, and encephalitis, renal failure, internal organ hemorrhage, cardiac arrhythmia, acute respiratory failure, ascites and liver injury, and bone marrow failure.

Lifileucel has a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. It also has warnings/precautions for hypersensitivity reactions. 

REFERENCE

1. Amtagvi (lifileucel), Iovance, February 2024. Available at https://www.fda.gov/media/176417/download?attachment. Accessed February 27, 2024.