FDA requires new warning for Penn-pioneered CAR-T therapy products

The United States Food and Drug Administration issued a new warning linking increased cancer risk to CAR-T cancer therapy, a treatment pioneered at Penn.

As of Jan. 23, the FDA is requiring a new boxed warning on CAR-T therapy products because of their link to the development of secondary cancers after initially opening an investigation in November 2023. Penn Medicine plans to continue offering the treatment to patients, according to a statement to The Daily Pennsylvanian.

Chimeric antigen receptor (CAR) T cell immunotherapy modifies the immune cells — known as T cells — of the patient to create CAR proteins that can target and kill their own cancer cells. Hundreds of patients at Penn Medicine — and more than 20,000 patients worldwide — have been treated with the technique since 2010, according to David Porter, the director of cell therapy and transplantation at Penn Medicine’s Abramson Cancer Center.

The FDA statement upon the opening of the investigation in November 2023 said that the overall benefits of CAR-T therapy products outweighed their potential risks for their approved uses. 

“We believe — even with these concerns and as the FDA has noted — that the potential benefits of CAR-T cells for these patients will far outweigh the very real, but small risk of secondary T cell cancers,” David Porter wrote to the DP. Porter added that the treatment is given to patients who have already been treated in other ways, most of whom are “facing dire prognoses."

While Porter said that the FDA’s required safety label warning does not change the way Penn Medicine doctors view this treatment, he believes that it will raise awareness of the treatment’s potential risks and help patients and physicians make educated decisions about treatment options.

“We will continue to offer these therapies to appropriate patients in need and work with each patient to provide the best possible options and treatment plans for their specific cancer type and care goals,” Porter wrote.

This new requirement was issued to five companies producing CAR-T therapy products — Bristol-Myers Squibb, Juno Therapeutics, Janssen Biotech of Johnson & Johnson, Novartis, and Kite Pharma. These companies were also ordered to monitor patients for the development of secondary cancers and report new cases back to the FDA.

A statement from FDA spokesperson Carly Kempler to NBC News said that the new requirement was implemented due to 25 reports to the FDA of previous CAR-T patients developing blood cancers. In addition, two abstracts were published in Blood citing an association between this therapy and increased cancer risk.

These warnings state that T-cell malignancies, which developed in patients treated with CAR-T therapy, have resulted in hospitalization and death. The boxed warning — colloquially called a “black box warning” — is the strongest safety label offered by the FDA. 

One of the new requirements in this FDA-issued warning is for drugmakers to follow up with patients receiving this therapy for 15 years — which Porter told the DP that Penn Medicine doctors had already been doing.

A Novartis spokesperson told NBC News that the company has not found “sufficient evidence” to support the link between secondarily-developed cancers and this therapy, but will work with the FDA to take the appropriate steps regarding labels.

Penn researcher Carl June led the Penn Medicine team that first used CAR-T cell therapy to treat adult leukemia patients in 2010, and later partnered with Swiss pharmaceutical company Novartis to continue CAR-T cell therapy research. The first CAR-T therapy — which was manufactured by Novartis — was approved by the FDA in 2017 for the treatment of pediatric and young adult patients with B-cell acute lymphoblastic leukemia.

"I have to keep pinching myself to see that this happened," June said to The New York Times in 2017. "It was so improbable that this would ever be a commercially approved therapy, and now it’s the first gene therapy approved in the United States. It’s so different from all the pharmaceutical models. I think the cancer world is forever changed."