Monday, May 20

FDA issues warnings about cancer risk linked to CAR-T therapies

The Food and Drug Administration requires companies that make specialized cancer therapies known as CAR-T to add a warning in a box that the treatments themselves can cause tumors.

The agency noted that the benefits still outweigh the risks of the therapy, which involves removing a type of white blood cell — T cells — and then genetically engineering it to create proteins called chimeric antigen receptors (CARs). . The engineered cells, reinfused into the patient’s blood, allow T cells to attach to tumor cells and kill them.

But the therapies, which primarily treat blood cancers including multiple myeloma, already carried a warning about dangerous immune responses and neurological risks. And the new warning follows reports of about 25 cases of secondary cancers that federal health officials and others suspected were caused by CAR-T treatments, although further investigation may be needed to establish a definitive link. The therapy has been used by at least 27,000 people patients since it was first approved by the FDA in 2017, the agency said.

Cancer patients who receive CAR-T treatments tend to have few options left and are unlikely to change course even with the new warning, said Dr. John DiPersio, an oncologist at Washington University in St. Louis.

“The risk of not doing this therapy for most patients who receive it is rapid disease progression or certain death,” he said.

The FDA raised concerns about the treatments’ adverse effects late last year.

In letters dated Jan. 19, the agency outlined warnings that some of the CAR-T therapy companies will include, which were also ordered to monitor patients for secondary cancers and report any to the FDA. Secondary cancers can lead to hospitalizations or death, the agency noted, requiring drug companies to provide warnings on drug labels that secondary cancers “may present as early as weeks after infusion and could include fatal outcomes.”

The FDA sent letters to these companies: Bristol-Myers Squibb, maker of Abecma; Juno Therapeutics, a Bristol-Myers Squibb company, maker of Breyanzi; Johnson & Johnson’s Janssen Biotech, maker of Carvykti; Novartis, by Kymriah; and Kite Pharma, from Yescarta.

Given the dire prognoses of patients considering CAR-T therapies, Dr. DiPersio said, the new warning amounts to “much ado about nothing.” He said he hopes the news doesn’t chill further investment or studies into treatments for other serious medical conditions. Some drugmakers are studying the use of CAR-T therapy to treat lupus, an autoimmune disease.

“We cannot create such a scary environment that companies and investigators turn this approach away because it is deemed too dangerous, because it is not,” he said.

Financial analysts had also predicted little fallout, Brian Abrahams, an analyst at RBC Capital Markets, said in an email.

“It’s still a very rare side effect,” he said. “These are sick patients receiving these therapies, and most CAR-T treatments have shown very clear benefits, including prolonged survival, so we would not expect these label changes to materially reduce the use of the agents.”