Response To FDA Black Box Warning

The FDA has launched an investigation into the risk of T-cell malignancies following CAR-T cell immunotherapies, which involve genetically engineering T cells to kill cancer cells. While CAR-T cell therapy has shown impressive results in treating B cell cancers, there are concerns about the long-term risks, including the development of secondary malignancies. The potential risks include changes in gene expression and the production of replication-competent viruses. However, this decision to investigate has led to a wave of confusion among the cell & therapy community.

If the risk of CAR-T cell-related malignancies is found to be serious, the existing class warning may be elevated to a black box warning. This would likely have little impact on current CAR-T cell products, which are already labeled with black box warnings for more frequent severe adverse events, such as CRS and neurological toxicity. New CAR-T cell products currently in development for cancer treatment are also unlikely to face unexpected obstacles from this investigation. Using healthy donor cells to create CAR-T cells and improving the pre-infusion conditioning of patients could potentially address these issues.

The FDA's investigation emphasizes the importance of ensuring the safety and efficacy of CAR-T cell therapy. This investigation also represents the coming of age of CAR-T cell therapy, rather than an unnecessary attempt to hold back potential therapies. Since CAR-T cells are becoming more widely available to cancer patients and beyond, the FDA is playing its role as the protector and educator of patients and healthcare workers by identifying potentially serious risks of CAR-T cell products. Review key areas and questions concerning the FDA’s recent announcement in the interest of the CGT scientific and research community.