The Food and Drug Administration told several drug companies this week that they needed to add a boxed warning, which is the agency’s strongest safety label, to the ordering information for CAR-T therapy, a type of cancer treatment. The warning said that the treatment itself may raise a person’s risk of getting cancer.
An FDA spokesperson, Carly Kempler, said that even though the products were warned about, “the overall benefits of these products continue to outweigh their potential risks.”
Kempler said that reports of rare blood cancers in people who had previously received CAR-T treatment led the government to decide to change the labels. She said that as of Monday, 25 reports of blood cancers in CAR-T patients had been sent to the government.
Bruce Levine, a professor of cancer gene therapy at the University of Pennsylvania, said that two abstracts published late last year in the journal Blood also mentioned a possible cancer risk with CAR-T therapy. He said that this likely “forced the FDA’s hand.”
CHImeric antigen receptor T cell therapy, or CAR-T treatment, treats some types of blood cancer with the patient’s immune cells. These types of cancer include leukemia, multiple myeloma, and lymphoma. It includes taking immunity cells, in this case, T cells, from the patient, changing their genes in a lab so that they can attack cancer cells, and then putting the changed cells back into the patient.
Experts say it works very well in situations that are hard to treat. In 2022, doctors who had used CAR-T to treat two people with leukemia ten years before said it was safe to say that the treatment had cured them.
“This changes the way we think about treating lymphoma and other illnesses,” said Dr. Matthew Frigault, who is in charge of the Cellular Immunotherapy Program at Boston’s Massachusetts General Hospital.
Novartis’ Kymriah, the first CAR-T treatment, was approved by the FDA in 2017. And since then, five more have been let go.
Bristol Myers Squibb made Abecma and Breyanzi; Gilead Sciences’ Kite Pharma made Yescarta; Johnson & Johnson made Carvykti; and Novartis made Kymriah. The FDA sent letters to the companies that made the drugs saying they had to propose label changes in 30 days to include a warning that CAR-T therapy can sometimes raise the risk of rare blood cancers. Kite Pharma did not get a letter about Tecartus, the sixth CAR-T drug.
If the drug companies don’t agree, they can send a response stating why the rules don’t need to be changed.
The company, Novartis, told NBC News that it has not found “sufficient evidence” to suggest a link between its treatment, which has been used in more than 10,000 people, and cancer. A business representative did say that they would work with the FDA to make changes to the label that are “appropriate.”
Johnson & Johnson and Gilead Sciences both said that they would work with the FDA to make changes to their labels.
Bristol Myers Squibb said in a statement that the company is thinking about “next steps” after receiving the FDA’s warning, even though the company has not seen any cases of cancer linked to its treatment.
“Patient safety is our top priority,” the representative said.
In what ways could CAR-T treatment lead to cancer?
Still, it’s not clear how CAR-T could cause cancer if it does.
Frigault of Mass General said, “We don’t know if this is casual, which means we don’t know for sure that the CAR-T cells in the tumor have caused this.”
CAR-T therapies are still pretty new: Frigault said that the FDA has told the companies that make the goods to do follow-up studies every 15 years to see how likely it is that people will get another cancer after treatment. (2ndary cancers are cancers that can happen after treatment.)
According to him, the FDA “is not saying that every single case they’ve reported has clearly shown CAR-T has led to this.” Instead, they are saying that there may be a link.
“The FDA does this.” “They await a sign,” he said.
Blood and cancer doctor Dr. Hemant Murthy of the Mayo Clinic in Jacksonville, Florida, said that the chance of CAR-T causing cancer is very low.
The FDA says that more than 27,000 doses of CAR-T treatment have been given in the U.S.
Murthy said, “I don’t think this will change practice too much.”
Dr. Saad Usmani, a myeloma doctor and cell therapist at Memorial Sloan Kettering, said that the change to the label should support what doctors already do, which is to talk to patients about the risk of getting another cancer after treatment for their first cancer.
Usmani said that other cancer treatments, like chemotherapy and radiation, also increase the chance of getting a second cancer.
“The change is likely because of recent reports, though it only happens very rarely,” he said.
Associate professor of medicine at Harvard Medical School and head of the Cellular Immunotherapy Program at Massachusetts General Hospital, Dr. Marcela Maus, said that doctors might be more careful, but it probably won’t make a big difference in how they do their jobs.
She said, “We need to take care of the cancer they have now, so I don’t think it will be very different.”