PATIENTS WITH ADVANCED MELANOMA that has progressed despite previous treatments now have a new option: Amtagvi (lifileucel), a tumor-infiltrating lymphocyte (TIL) therapy. The Food and Drug Administration (FDA) announced the accelerated approval of Amtagvi on Feb. 16.

“It’s important to have as many potential treatment options as possible and TIL therapy adds to the armamentarium of tools we have as oncologists to try to help people with advanced melanoma live longer,” says Rodabe N. Amaria, an oncologist who specializes in advanced stage melanoma at University of Texas MD Anderson Cancer Center in Houston, who was not associated with the study cited in the approval.

TIL therapy is now approved for patients with metastatic melanoma or melanoma that can’t be surgically removed that has been previously treated with a PD-1 blocking antibody and, in cancers that have a BRAF V600 mutation, a BRAF inhibitor.

How TIL Therapy Works

Amtagvi and other TIL therapies use the body’s own immune cells to infiltrate and eradicate cancer. Scientists have for decades seen the therapeutic potential of immune cells found inside of tumors and have been trying to find a way to capture that natural process to improve treatment, says Amod Sarnaik, a surgical oncologist at Moffitt Cancer Center’s Melanoma Center of Excellence in Tampa, Florida. Sarnaik and his Moffitt Cancer Center team were involved in research that eventually led to Amtagvi’s FDA approval. “We discovered that if we can remove a portion of the patient’s tumor, we can culture the natural immune cells, these tumor-infiltrating lymphocytes that infiltrate the tumor, and use that as a form of treatment,” Sarnaik says.

TIL therapy is a lengthy, multistep process that can take up to eight weeks. Like CAR T-cell therapy, TIL therapy involves taking healthy cells out of the body and processing them in a lab to fight cancer. “But TIL therapy doesn’t require genetically modifying the immune cells [like CAR T-cell therapy]. We rely on the natural process of tumor rejection and amplify it,” Sarnaik says.

TIL therapy starts with surgery to remove one to two cubic centimeters of melanoma tumor tissue. The tissue specimen is sent to Amtagvi’s manufacturer, Iovance Biotherapeutics, where the patient’s normal circulating immune cells are extracted from the tumor. “Coaxing these immune cells out of the tumor requires the use of interleukin-2 (IL-2),” Sarnaik says, which are small proteins made by immune system T cells that control the growth and activity of other immune system cells. “It requires a 22-day manufacturing period,” Sarnaik says.

After the T cells are returned from the manufacturer, patients are hospitalized for five to 10 days. There, they have chemotherapy before receiving a single TIL infusion, which takes roughly 90 minutes, followed by an IL-2 infusion to support the growth of TILs.

How effective is TIL therapy at killing melanoma? The study cited in the approval, published in the November 2022 issue of Journal for ImmunoTherapy of Cancer, found that treatment with Amtagvi resulted in a 31.4% response rate. In that analysis, patients who showed a response were followed for 13.9 months. “But these patients have continued to be followed for almost four years and continue to be cancer-free,” Sarnaik, an author on the study, says. Overall, “the treatment seems to work quite well in patients who achieve a response.”

Risks of TIL Therapy

“TIL therapy is rough on the body,” Sarnaik says. Patients can expect the traditional side effects of receiving chemotherapy, including nausea, vomiting, fatigue and rashes. IL-2 therapy can also cause high fevers of 103 degrees or higher, accompanied by shaking, chills and feeling run down. It takes about a week following treatment for people to return to feeling normal, Sarnaik says. Moreover, the treatment can be deadly. In one clinical trial, 7.5% of people who received the treatment died from it. The mortality rate is stated on the product’s package insert.

“TIL therapy is something patients have to be carefully selected for because it’s a very intensive therapy,” Amaria says. “But hopefully, the T cells take root in the immune system and provide long-lasting benefits.”

After being hospitalized for treatment, patients don’t require any more infusions, unlike other melanoma therapies, which require treatments for months. “It’s one and done, which is amazing,” Amaria says. “People with advanced melanoma who respond to TIL therapy can really get their lives back.”

Sandra Gordon is a medical writer in Stamford, Connecticut.