FDA Investigating ‘Serious Risk’ of Secondary Malignancy Linked to BCMA- or CD19-Directed CAR-T Immunotherapies
29 November 2023
Regulatory & Standards
The FDA is investigating the identified risk of T cell malignancy with serious outcomes following reports received from clinical trials and from data sources of postmarketing adverse event (AE). These include hospitalization and death. The FDA will also be evaluating the need for regulatory action.
The FDA has received reports of T cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR-T cell immunotherapies.
As determined by the FDA, the risk of T cell malignancies is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR-T cell immunotherapies. T cell malignancies have occurred in patients treated with several products in the class.
The following currently approved products in this class are:
Integrating vectors such as lentiviral or retroviral vectors within cell and gene therapy has the potential risk of developing secondary malignancies. For all approved BCMA-directed and CD-19-directed genetically modified autologous T cells, these risks are labeled as a class warning in the United States prescribing information (USPIs).
The approval process for these products included postmarketing requirements (PMRs) under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (FDCA). These requirements mandated the conduct of 15-year long-term follow-up observational safety studies to assess the long-term safety of the products, and to determine the risk of secondary malignancies occurring after treatment.
While the benefits of these products still outweigh their potential risks for their approved uses, the FDA is currently investigating the identified risk of T cell malignancies. These malignancies can lead to serious outcomes, such as hospitalization and even death. As a result, the FDA is evaluating whether regulatory action is necessary.
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