The FDA says treating cancer with CAR-T therapy may increase the risk of cancer

The FDA says treating cancer with CAR-T therapy may increase the risk of cancer

The Food and Drug Administration this week asked several drug makers to add a warning — the agency’s strongest safety label — to the prescribing information for a type of cancer treatment called CAR-T therapy, saying the treatment itself may increase a person’s risk of developing cancer.

Despite the warning, “the overall benefits of these products still outweigh their potential risks,” said Carly Kempler, a spokeswoman for the US Food and Drug Administration.

The agency’s decision to update the ratings was based on the reports The rare blood cancers are in patients who have previously received CAR-T therapy, Kempler said. As of Monday, the agency had received 25 reports of leukemia cases in CAR-T patients, she said.

In addition to reports to the FDA, two abstracts published late last year in the journal Blood also pointed to a potential cancer risk associated with CAR-T therapy, said Bruce Levin, a professor of cancer gene therapy at the University of Pennsylvania. Which “likely forced the FDA.”

CAR-T — or chimeric antigen receptor T cells — therapy uses a patient’s own immune cells to treat some types of blood cancer, such as leukemia, multiple myeloma, and lymphoma. It involves harvesting immune cells – in this case T cells – then genetically modifying them in the laboratory to make them target cancer cells, and finally transplanting them back into the patient.

Experts said that it has proven highly effective in cases that are difficult to treat. In 2022, doctors who treated two leukemia patients with CAR-T a decade ago said it was fair to say the treatment had cured the patients of the disease.

“This is a game-changer when we think about treating lymphoma and other diseases,” said Dr. Matthew Frigault, clinical director of the cellular immunotherapy program at Massachusetts General Hospital in Boston.

The first CAR-T treatment, Novartis’ Kymriah, received FDA approval in 2017. Since then, five more treatments have been approved.

Manufacturers of five drugs – Bristol-Myers Squibb, ABECMA and Brianzi; Gilead Sciences Kite Pharma for Yescarta; Johnson & Johnson Carfacti; Novartis, on behalf of Kymriah, received letters from the FDA stating that they must submit proposed changes to the label within the next 30 days to note that, in rare cases, CAR-T therapy can increase the risk of rare blood cancers. (Kite Pharma did not receive a letter regarding its sixth CAR-T drug, Tecartus.)

If drugmakers disagree, they can instead offer a rebuttal explaining why the change isn’t needed.

In a statement to NBC News, a Novartis spokesperson said the company had found “insufficient evidence” to support a link between the cancer and its treatment, which has been used in more than 10,000 patients. However, the spokesperson said the company will work with the FDA to update its branding “appropriately.”

Spokespeople for Johnson & Johnson and Gilead Sciences also said the drugmakers would work with the agency to update their labels.

A Bristol-Myers Squibb spokesman said the company is evaluating “next steps” after the FDA notification, even though it has not seen any cancer cases linked to its treatment.

“Patient safety is our top priority,” the spokesman said.

How can CAR-T therapy cause cancer?

However, there is still a question about how CAR-T causes cancer, if it does at all.

“Actually, we don’t know if this is incidental, that is, we don’t know for sure that it was the CAR-T cells in the tumor that led to this,” said Mass General’s Frigault.

CAR-T therapies are still relatively new: Frégault noted that the FDA has asked product makers to conduct 15-year follow-up studies to evaluate the potential risk of secondary cancer after treatment. (Secondary cancers are cancers that can arise from treatment.)

The FDA “is not saying that every one of the cases it reported clearly showed that CAR-T led to this, but there may be more of a connection,” he said.

“That’s what the FDA does. They’re looking for a signal,” he added.

If CAR-T causes cancer, the risk is likely very small, said Dr. Hemant Murthy, a hematologist and oncologist at the Mayo Clinic in Jacksonville, Florida.

More than 27,000 doses of CAR-T therapy have been administered in the United States, according to the FDA.

“I don’t really see this impacting much of the practice,” Murthy said.

The label change should support doctors’ current practice of discussing the risk of developing secondary cancers after cancer treatment with patients, said Dr. Saad Usmani, a myeloma physician and cytopathologist at Memorial Sloan Kettering.

Othmani noted that other cancer treatments, such as radiotherapy and chemotherapy, also carry the risk of developing secondary cancers.

He said: “Change is expected in light of recent reports, although the infection rate is very low in such cases.”

Doctors may be more cautious, but likely won’t change much in their practice, said Dr. Marcella Moss, an assistant professor at Harvard Medical School and director of the cellular immunotherapy program at Massachusetts General Hospital.

“We need to manage their cancer now, so I can’t imagine it’s any different,” she said.

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