FDA Requires CAR-T Cancer Warnings Be Added For All Drugs in the Class

Cancerous tumors can develop within weeks after receiving CAR-T drug infusions, some of which can be fatal, the FDA warns.

Federal drug regulators are requiring all chimeric antigen receptor T-cell therapy (CAR-T) drugs, such as Carvykti,Abecma, Kymriah, and Tecartus, to carry black box warnings about an increased risk of cancer.

On January 19, the U.S. Food and Drug Administration (FDA) issued six safety labeling change notification letters to CAR-T manufacturers, indicating their drugs would have to carry the most stringent label warning the agency can require.

The agency warns that side effects of CAR-T drugs may include a risk of T cell malignancies, which can result in serious health consequences, including hospitalization and death.

CAR-T Cancer Warnings Extended Beyond Carvykti

The requirements come about a month after the FDA announced that Carvykti would be required to carry a black box label warning about an increased risks of secondary cancers, including myelodysplastic syndrome and acute myeloid leukemia. That Car-T therapy is manufactured by Legend Biotech Corporation, which produces the drug in cooperation with Johnson & Johnson.

Carvykti was also included in the batch of letters sent out last week, along with the makers of Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), and Yescarta (axicabtagene ciloleucel).

The CAR-T treatments were approved under a 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 an investigation into secondary cancer risks with CAR-T treatments, impacting the entire class, and the agency indicated that review is still ongoing.

CAR-T Treatment Black Box Warnings

“(W)e have become aware of the risk of T cell malignancies, with serious outcomes, including hospitalization and death, following treatment with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies,” the agency wrote to drug manufacturers. “FDA identified postmarketing adverse event and clinical trial reports describing occurrence of mature T cell malignancies, including CAR-positive tumors, following treatment with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies.”

The FDA determined the drugs should carry boxed warnings in the full prescribing information and highlights section, as well as add new sections to the Warnings and Precautions, Adverse Reactions, and Patient Counseling Information on the drugs’ labels and medication guides.

They indicate that T cell malignancies may occur after treatment, some of which may present as tumors within weeks of receiving an infusion, and some of which may result in death.

The manufacturers have 30 days from January 19 to submit proposed changes to the drugs’ labels.

FDA Recommends CAR-T Patient Monitoring

As a result of the risks associated with side effects of Carvykti and other CAR-T treatments, 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.