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FDA approves groundbreaking treatment for advanced melanoma

By Erika Edwards, Anne Thompson and Marina Kopf

Feb 20, 2024

TIL therapy shrank tumors in about a third of patients who had run out of treatment options, according to a clinical trial.

The Food and Drug Administration on Friday approved a new cancer therapy that could one day transform the way a majority of aggressive and advanced tumors are treated.

The treatment, called Amtagvi, from Iovance Biotherapeutics, is for metastatic melanoma patients who have already tried and failed other drugs. It’s known as TIL therapy and involves boosting the number of immune cells inside tumors, harnessing their power to fight the cancer.

It’s the first time a cellular therapy has been approved to treat solid tumors. The drug was given a fast-track approval based on the results of a phase 2 clinical trial. The company is conducting a larger phase 3 trial to confirm the treatment’s benefits. The therapy’s list price — the price before insurance and other potential discounts — is $515,000 per patient. 

“This is going to be huge,” said Dr. Elizabeth Buchbinder, a senior physician at Dana-Farber Cancer Institute in Boston. Melanoma is “not one of those cancers where there’s like 20 different” possible treatments, she said. “You start running out of options fast.” 

Friday’s approval is only for melanoma, the deadliest form of skin cancer, but experts say it holds promise for treating other solid tumors, which account for 90% of all cancers. 

“It is our hope that future iterations of TIL therapy will be important for lung cancer, colon cancer, head and neck cancer, bladder cancer and many other cancer types,” said Dr. Patrick Hwu, chief executive of the Moffitt Cancer Center in Tampa, Florida. Moffitt has been involved with Iovance’s clinical trials of TIL therapy.

TIL stands for tumor-infiltrating lymphocytes, which are immune cells that exist within tumors. But there are nowhere nearly enough of those cells to effectively fight off cancer cells. TIL therapy involves, in part, extracting some of those immune cells from the patient’s tumor and replicating them billions of times in a lab, then reinfusing them back into the patient. 

It’s similar to CAR-T cell therapy, where healthy cells are taken out of a person’s body and then modified in a lab to fight cancers. That’s usually used for hard-to-treat blood cancers such as leukemia and lymphoma. With TIL therapy, the cells used are already programmed to recognize cancer — no lab modifications needed — they just need a boost in numbers to fight it. 

Like CAR-T, TIL therapy is a one-time treatment, though the entire process can take up to eight weeks. The TIL cells are first harvested from the tumor through a minimally invasive procedure and then grown and multiplied in the lab, a process that takes 22 days, according to Iovance. 

While that’s happening, patients are given chemotherapy to clear out their immune cells to make room for the billions of new melanoma-fighting TIL cells. Once the TIL cells are reinfused back into the body, patients get a drug called interleukin-2 to further stimulate those cells. 

Hwu said that most side effects in patients undergoing TIL therapy are not from the reinfusion of cells, but from the chemotherapy and the interleukin-2. These can include nausea and extreme fatigue, and patients are also vulnerable to other illnesses because the body is depleted of disease-fighting white blood cells. 

Putting billions of cells back into the body is not entirely risk-free, however, said Dr. William Dahut, chief scientific officer of the American Cancer Society. It’s possible that the body’s immune system could overreact in what’s known as a cytokine storm, which can cause flu-like symptoms, low blood pressure and organ damage. “There are risks for immune-related side effects, which could be serious,” he said.

Common side effects associated with Amtagvi can include abnormally fast heart rate, fluid buildup, rash, hair loss and feeling short of breath, the FDA said.

Those side effects can be managed, said Dr. Steven Rosenberg, chief of the surgery branch at the National Cancer Institute. “They’re a small price to pay for a growing cancer that would otherwise be lethal.”

Overall, Dahut said the approval of TIL therapy is “meaningful.”

“What’s nice about this is that patients will receive a wide variety of tumor fighting lymphocytes that will be able to have the capacity to overcome resistance and actually be a living therapy over time, too, to target additional cancer cells should they develop,” Dahut said.

In addition to melanoma, Dahut said that TIL therapy is most likely to be useful in cancers that respond to drugs that “take the brakes off the immune system,” called checkpoint inhibitors.

“Those would be things like non-small cell lung cancer, kidney cancer, maybe bladder cancer, that we know are responsive to immune-based therapies to begin with,” he said. “Many of those patients relapse, so another immune-based therapy that works in a different way, seems to me, the most likely way for this to be effective.”

Much more research is needed, and it may be years before TIL therapy is approved for other types of cancer.


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