FDA Adds Black Box Cancer Warning to Carvykti Car-T Treatment

Clinical studies and post-marketing surveillance has linked side effects of Carvykti to a more than 10% increased risk of blood cancer.

The CAR-T cancer treatment Carvykti must carry a new black box label warning, alerting doctors and patients to the risk that users may develop secondary cancers.

Carvykti (ciltacabtagene autoleucel) was first approved by the FDA in 2022, for the treatment of multiple myeloma, but only after they have tried four or more prior types of therapy first. It belongs to a class of drugs known as chimeric antigen receptor T-cell therapy (CAR-T).

On December 22, the U.S. Food and Drug Administration (FDA) announced the new Carvykti label warnings, indicating that side effects of the cancer drug may increase the risk of secondary cancers, including myelodysplastic syndrome and acute myeloid leukemia.

The manufacturer, Legend Biotech Corporation, which produces the drug in cooperation with Johnson & Johnson, acknowledged the new requirements in a Securities and Exchange Commission (SEC) filing on December 21.

CAR-T Side Effects Investigation

There are currently six FDA-approved CAR-T treatments, which include Carvykti, Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), and Yescarta (axicabtagene ciloleucel). These treatments were approved under the requirement that the FDA conduct a 15-year observational study to assess the potential for long-term adverse health outcomes and secondary malignancies that could occur after treatment.

In late November, the FDA launched in investigation into secondary cancer risks with CAR-T treatements, impacting the entire class, and the agency indicated this week that review is still ongoing.

While CAR-T therapies already carry a warning of secondary cancer risks, the agency has been trying to determine if stronger warnings are needed for all of the medictations.

Carvykti Black Box Label Warning

This new Carvykti label update was announced less than one month into the agency’s investigation, and requires the drug to carry a black box warning, which is strongest label warning the FDA can require a drug to carry. According to the SEC filing, the new warning will indicate:

“Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred following treatment with CARVYKTI.”

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) events occurred in 10 out of 97 patients who received Carvykti treatment during a clinical trial and in post-marketing cases, suggesting secondary blood cancers develop in more than 10% of users. According to FDA data, nine of those 10 patients eventually died from bone marrow problems.

FDA Recommends Carvykti Patient Monitoring

As a result of the risks associated with side effects of Carvykti, the FDA recommends that patients or clinical trial participants receiving these treatments be monitored for the rest of their life by a health care professional for new cancers that may develop.

Patients and trial participants are urged to report any new malignancies they may develop following CAR-T treatment to the manufacturer, and obtain instructions on how to collect patient samples for testing purposes.

Individuals are also encouraged to report any adverse events experienced after receiving treatment, including T cell malignancies, to the FDA MedWatch Adverse Event Reporting Program.

For more information, medical professionals, investigators, patients, and caregivers may contact the FDA Center for Biologics Evaluation and Research (CBER) by email at ocod@fda.hhs.gov.