Several pharmaceutical companies have been instructed by the US Food and Drug Administration (FDA) to add a boxed warning – the agency’s strongest safety label – to the prescribing information for the cancer treatment CAR-T therapy, saying the treatment itself may increase a person’s risk of cancer.
Spokesperson Carly Kempler said that, despite the warning, “the overall benefits of these products continue to outweigh their potential risks”, reports NBC News.
The decision to update the labels was based on reports of rare blood cancers in patients who had undergone CAR-T therapy, Kempler said. As of last week, the agency had received 25 reports of the blood cancers in CAR-T patients, she said.
Bruce Levine, a professor in cancer gene therapy at the University of Pennsylvania, said that in addition to the reports submitted to the FDA, two abstracts published late last year in the journal Blood also cited a potential cancer risk associated with CAR-T therapy, which probably “forced the FDA’s hand”.
CAR-T – or chimeric antigen receptor T cell – therapy uses a patient’s own immune cells to treat certain blood cancers, such as leukaemia, multiple myeloma and lymphoma. It involves harvesting the immune cells, in this case, T cells, then genetically altering them in a lab to make them target cancer cells, and finally re-infusing them back into the patient.
It’s proved to be highly effective in hard-to-treat cases, experts said. In 2022, doctors who had treated two leukaemia patients with CAR-T a decade ago, said it was fair to say the therapy had cured the patients of the disease.
“This has been a game changer when we think about treating lymphoma and other diseases,” said Dr Matthew Frigault, clinical director of the Massachusetts General Hospital Cellular Immunotherapy Programme.
The first CAR-T therapy, Novartis’ drug Kymriah, received FDA approval in 2017. Since then, another five have been approved.
FDA Letters were sent to the makers of the drugs – Bristol Myers Squibb, for Abecma and Breyanzi; Gilead Sciences’ Kite Pharma, for Yescarta and Tecartus; Johnson & Johnson’s Carvykti; and Novartis, for Kymriah – telling them to submit proposed label changes in the next 30 days to note that, in rare cases, CAR-T therapy can increase the risk of rare blood cancers.
If the companies disagree, they can, instead, submit a rebuttal explaining why a change isn’t needed.
A spokesperson for Novartis told NBS News the company has not found “sufficient evidence” to support a link between cancer and its treatment, which has been used in more than 10 000 patients. However, the company would work with the FDA to update its label “appropriately”.
Spokespersons for J&J and Gilead Sciences also said they would update their labels.
Bristol Myers Squibb is evaluating “next steps” after the FDA’s notice, although it has not seen any cancer cases associated with its treatment.
How might CAR-T therapy cause cancer?
Still, there’s the question of how CAR-T could cause cancer – if it does at all.
“We actually don’t know whether this is causal, meaning, we don’t know for a fact that the CAR-T cells in the tumour have led to this,” said Frigault, of Mass General.
CAR-T treatments are still relatively new: Frigault said the FDA has required that the makers of the products conduct 15-year follow-up studies to assess the potential risk of secondary cancers after treatment. (Secondary cancers are cancers that can arise from treatment.)
“The FDA is not saying every single one of the cases it’s reported has clearly shown CAR-T has led to this,” he said, “but more that there may be an association. This is what the FDA does. It looks for a signal.”
More than 27 000 doses of CAR-T therapy have been administered in the US, according to the FDA.
NBC article – FDA says cancer treatment CAR-T therapy may increase risk of cancer (Open access)
See more from MedicalBrief archives:
CAR-T cell therapy for leukaemia associated with less dangerous side effects
FDA probes safety of CAR-T therapies
Decade-long leukaemia remissions with CAR T-cell therapy – Landmark study