FDA to Investigate Risk of T-Cell Malignancy After CAR T-Cell Therapy

The FDA has announced that it will be investigating the risk of T-cell malignancies in patients that have received B cell maturation antigen (BCMA)-directed or CD19-directed autologous chimeric antigen receptor T cell (CAR T)nimmunotherapies.¹

The FDA stated that it has received reports from clinical trials and/or data sources of cases of T-cell malignancies that developed after CART treatment. The FDA has determined that the apparent risk is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T-cell therapies, including the approved therapies

Abecma (idecabtagene vicleucel)

Breyanzi (lisocabtagene maraleucel)

Carvykti (ciltacabtagene autoleucel)

Kymriah (tisagenlecleucel)

Tecartus (brexucabtagene autoleucel)

Yescarta (axicabtagene ciloleucel).

According to the FDA Adverse Event Reporting System (FAERS) database, there have been 12 patients who developed a T-cell lymphoma following treatment with an FDA approved CAR T-cell therapy.

In its statement, the FDA stated that the overall benefits of these products continue to outweigh their potential risks for their approved uses. The potential risk of developing secondary malignancies is labeled as a class warning in the US prescribing information for all gene therapy products with integrating vectors (lentiviral or retroviral). All initial approvals of these products require sponsors to conduct 15-year long-term follow-up studies to assess safety and the risk of secondary malignancies.