The Food and Drug Administration (FDA) is requiring a boxed warning on all existing CAR-T cancer treatments following a review of reports that the therapies themselves can increase the risk for some secondary cancers.
In letters to the manufacturers of all six currently available CAR-T therapies dated Jan. 19, the FDA said the prescribing information will need to include so-called black box warnings, the most serious type for any medication.
CAR-T is a gene therapy that works by extracting white blood cells known as T-cells from a patient, reengineering them in a lab to attack cancer cells and then infusing them back into the body.
The treatments impacted include Abecma and Breyanzi from Bristol Myers Squibb, Carvykti from Johnson & Johnson (J&J) and Legend Biotech, Kymriah from Novartis and Tecartus and Yescarta from Gilead.
The required warning label comes less than two months after the FDA made public an investigation into reports of T-cell malignancies — types of cancer in blood cells — including lymphoma and leukemia in people who received treatment with CAR-T therapies.
The FDA at the time said it determined that the risk was “serious” and applicable to all currently approved CAR-T products. Some of the disorders resulted in hospitalization and death.
The agency is allowing the therapies to stay on the market, a sign their benefits continue to outweigh the risks. The companies have 30 days to submit proposed changes to the label.
Kymriah, the first CAR-T therapy to get FDA approval, has been on the market since 2017 to treat leukemia.
The FDA’s initial approvals of CAR-T products included requirements to conduct 15-year-long follow-up safety studies to assess the long-term safety and the risk of secondary malignancies occurring after treatment.
Novartis and J&J separately said they would work with the FDA to update the prescribing information for Kymriah and Carvykti.
Novartis added it “has not found sufficient evidence to support the causal relationship between Kymriah and secondary T-cell malignancies to date and remains confident in the favorable benefit/risk profile of Kymriah.”
A spokesperson for Gilead similarly said the company will work with the FDA on next steps but is “not aware of evidence to date establishing that treatment with Yescarta or Tecartus has a causal role in the development of malignancies of T-cell origin.”