FDA Found 22 Cases of Cancer Linked to CAR-T Treatments: Report

Genetic sequencing appears to confirm that some cases of cancer have a direct connection to CAR-T cell transgenes used in the medications, the FDA reports.

Federal regulators have released data that explains the recent decision to require black box warnings on chimeric antigen receptor (CAR-T) cell therapies, like Carvykti and Abecma, indicating that at least 22 cases of secondary cancer have been linked to the class of medications through the end of last year.

Researchers from the U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research published their findings in the New England Journal of Medicine on January 24, just days after the agency required all six drugs in the class to update their label warnings to include data on the CAR-T cancer risks.

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.

The FDA determined the drugs should carry prominent boxed warnings in the full prescribing information and highlights section, as well as new sections in the Warnings and Precautions, Adverse Reactions, and Patient Counseling Information of the drugs’ labels and medication guides, which describe the link between CAR-T and cancer.

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.

The FDA began its investigation into CAR-T cancer risks in November.

“As of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers that occurred after treatment with CAR-T products,” FDA officials wrote in a Perspective piece in the medical journal. “Such cancers have included T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.”

The FDA indicates that there are 14 cases for which adequate data is currently available, and all manifested within two years of CAR-T treatment, ranging from one to 19 months.

Some of the cases are still under investigation, but cancer incidents have been reportedly linked to five of the six CAR-T cell drugs on the market, including Abecma, Breyanzi, Carvykti, Kymriah and Yescarta. The sixth drug, Tecarus, had no cases of cancer linked to it, but the FDA required it to also carry a black box warning anyway.

According to the report, in three cases where genetic sequencing was performed, the CAR transgene has been detected in the cancer, indicating that the drugs were probably involved in the development of T-cell cancer incidents.

The agency warns that the cases are still under investigation, and raised concerns that postmarketing reports may underestimate the number of cancer cases related to the drugs.

CAR-T Patient Monitoring Needed: FDA

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.

“It is important for clinicians caring for people who have received CAR T cells to report the occurrence of any new cancer,” the FDA investigators advised. “At this time, we recommend that patients and clinical trial participants who receive treatment with these products be monitored for new cancers throughout their lives, since – owing to the relatively recent widespread introduction of CAR-T products into clinical care – we don’t yet know how long after treatment people remain at risk for these adverse events.”

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.