IN AUGUST 2024, the Food and Drug Administration (FDA) granted accelerated approval for a T-cell receptor therapy to treat a rare cancer called synovial sarcoma—a soft tissue cancer that grows into the connective tissue near the joints. This cancer affects about 1,000 people—many of whom are young adults—in the U.S. each year. The median survival in people who are diagnosed with advanced synovial sarcoma is just 16.2 months, according to one study.

Tecelra (afamitresgene autoleucel or afami-cel therapy) is approved for people with inoperable or metastatic synovial sarcoma who have received prior chemotherapy and whose cancer expresses a protein called MAGE-A4. The approval was based on results from a phase II clinical trial published April 13, 2024, in the Lancet, which included 44 people with metastatic synovial sarcoma. In the study, 17 participants had a tumor response with a median response duration of about six months.

The treatment uses engineered T cells to target MAGE-A4, which is typically not found in normal tissue, says Sandra D’Angelo, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City who led the clinical trial. To be eligible for the treatment, patients must also have a specific immune system marker called HLA-A*02. This genetic marker, which is inherited from the parents and is detected with a blood test, is found in about a quarter of the U.S. population.

To start T-cell receptor therapy, a patient’s white blood cells are removed from the blood and sent to a lab where the T cells are genetically modified so they can identify MAGE- A4, D’Angelo explains. This engineering process to make the T cells takes about six weeks. “If someone has rapidly progressive disease, they may not have enough time to go through screening, manufacturing and getting the T cells,” D’Angelo says.

Once the engineered T cells are available, patients receive intensive chemotherapy that depletes existing T cells in the body to make room for the engineered cells. “It’s got pretty toxic chemotherapy as a necessary factor,” says George Demetri, a medical oncologist at Dana-Farber Cancer Institute in Boston, who is an author of the study. The overall survival benefit in patients who respond to the treatment is an extra four to six months, says Demetri, who notes that “it’s a lot to go through for a small amount of benefit.” He adds, “Some patients, having gone through this, could have the disease in control for a year or two.”

Despite side effects of treatment and the time it takes to engineer the T cells, Demetri sees T-cell receptor therapy as a promising development that could be applied to other cancers. And while the treatment response may not be as robust as researchers or patients hoped for in synovial sarcoma, he says, “it’s a starting point, and that’s why I actually do think the FDA did the right thing by giving it an accelerated approval.” The FDA grants accelerated approvals to drugs using surrogate endpoints—markers that predict clinical benefits—as opposed to more traditional measures like overall survival. In this case, the approval was based on tumor response. Demetri notes that, given the rarity of synovial sarcoma, a larger trial could take decades to complete.

MAGE-A4 is sometimes expressed in other malignancies like ovarian, bladder and lung cancers, D’Angelo says. However, “for all those other cancers, there’s a lot of other different effective therapies, so there’s a less pressing need” for treatment with Tecelra, she says. D’Angelo notes that new therapies aren’t typically tested in or approved for rare diseases. “I think that it’s amazing that a rare cancer like synovial sarcoma was the poster child for this effort,” she says.