Lifileucel (Amtagvi) a tumor-derived autologous T cell immunotherapy, for adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor.

Lifileucil is the first treatment for cancer that uses tumor-infiltrating lymphocytes, or TILs.

Lifileucel the first cellular therapy to be approved for a solid tumor, melanoma.

The use of lifileucel is for people with advanced melanoma that has gotten worse after treatment with certain immunotherapy drugs or targeted therapies.

As is the case with CAR T-cell therapy, another type of cellular therapy, lifileucel is made using a patient’s own T cells.

The cells are collected at the hospital where the patient is being treated but are sent away to be manufactured into the final treatment.

For the approved CAR T-cell therapies, the T cells are collected from a patient’s circulating blood.

For TIL therapy, by contrast, the T cells are collected from the patient’s tumor.

Safety and efficacy were evaluated in a global, multicenter, multicohort, open-label, single-arm trial in patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor. 

Lifileucel was administered following a lymphodepleting regimen consisting of cyclophosphamide 60 mg/kg daily with mesna for 2 days followed by fludarabine 25 mg/m2 daily for 5 days. 

Three to 24 hours after infusion, patients received IL-2 (aldesleukin) at 600,000 IU/kg every 8 to 12 hours for up to 6 doses in order to support cell expansion in vivo. 

The median administered lifileucel dose was 21.1× 109 viable cells. 


The median number of administered IL-2 (aldesleukin) doses was 6.

The main efficacy outcome measures were objective response rate (ORR) and duration of response (DoR). 

The median time to initial response to lifileucel was 1.5 months. 

ORR was based on 73 subjects who received lifileucel within the recommended dosing range of 7.5 x109 to 72×109 viable cells. ORR was 31.5% (95% CI: 21.1, 43.4) and median DoR was not reached (NR): 4.1 months, NR).

Contains a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. 

The most common adverse reactions (≥20%) in order of decreasing frequency were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

In a study of more than 70 participants who were treated with the lifileucel dose, nearly one-third had at least some reduction in the size of their tumors, and aa complete response in several participants.

About 40% of those whose cancer responded to lifileucel still had no progression of their cancer a year after receiving the one-time infusion treatment.

The recommended lifileucel dose is 7.5 x 109 to 72 x 109 viable cells.

These cells are collected from samples of tumor tissue, and have already proven that they can recognize and navigate to tumors,

Such recognition relies on the presence of specific abnormal proteins, or antigens, on the surface of the tumor cells.

TILs collected from a patient’s tumor are not genetically changed, there are steps taken during the manufacturing process, including mixing them with IL-2—to help them expand into billions of cancer-fighting immune cells.

In the days prior to receiving lifileucel, patients undergo a few rounds of high-dose “lymphodepleting” chemotherapy.

After the lifileucel infusion, they are given several doses of IL-2.

Long-lasting tumor responses to lifileucel

FDA’s approval was based on data from a group of 73 patients in the trial whose cancer had gotten worse despite treatment with a PD-1/PD-L1-targeted immune checkpoint inhibitor or a BRAF inhibitor and whose lifileucel dose was at least 7.5 billion cells.

Of the 48 people (31.5%) whose cancer responded to treatment with lifileucel, more than half have lived at least a year without any evidence of their cancer getting worse: About 10% of these responses are ongoing, and nearly all have lasted several years.

Only a few people whose cancer had spread to the brain or liver, which was the case for about half of the 153 patients, responded.

Responses were also unlikely in people who had larger tumor burdens—that is, a substantial amount of cancer in their body.

Lifileucil might be most effective if it’s given before the cancer has spread to many other parts of the body or individual tumors have become quite large.

All participants in the trial had side effects caused by the treatment, largely caused by the chemotherapy given before the lifileucel infusion and IL-2 given afterward.

The most common included anemia, high fevers, and substantial drops in levels of platelets and certain white blood cells.

TIL therapy does not appear to cause the often serious immune-related side effects commonly seen in people treated with CAR T-cell therapy, including cytokine release syndrome and neurologic effects.

A single treatment with lifileucel will cost $515,000.

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