The U.S. Food and Drug Administration (FDA) recently announced an investigation into whether Chimeric Antigen Receptor T-cell therapies (CAR T-therapies)—cell therapies approved for treating advanced cases of blood cancer—are causing secondary cases of cancer. The FDA is delving into incident reports of T-cell malignancies in patients who have received treatment with a cell therapy, coming from clinical trials or adverse event reports after market introduction.
The FDA has not associated the T-cell malignancy reports with specific therapies, but indicated that the risk applies to all currently approved therapies addressing either BCMA, a multiple myeloma target, or CD19, a target for cell therapies used in treating leukemias and lymphomas. The FDA’s statement said, “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action.”
The inquiry covers products such as Abecma and Breyanzi, developed by Bristol Myers Squibb; Carvykti from Johnson & Johnson; Kymriah from Novartis; and Tecartus and Yescarta from Gilead Sciences. You can read more about how CAR T-therapies are made here.
The manufacturing process involves introducing a gene using a viral vector, prompting the immune cell to express the antigen that targets cancer cells (referred to as the “CAR” in CAR T-therapy). However, there is a risk that this process can cause new mutations in the DNA leading to cancer, a phenomenon known as insertional mutagenesis. It is a known risk in cell and gene therapies using viral vectors.
Alongside the approval of these cell therapies, the FDA requires that companies continue monitoring patients for 15 years post-treatment to assess long-term safety, including the risk of developing secondary cancers. William Blair analyst Matt Phipps remains of the belief that patient risk remains low despite the FDA inquiry. His firm’s search of the FDA Adverse Event Reporting System revealed 12 reports of T-cell lymphoma, although these reports do not state whether they are CAR-positive lymphomas or the location of the CAR insertion.
As the FDA urges patients and clinical trial participants receiving CAR T therapies to be monitored for new cancers throughout their lifetime, it enlightens the crucial dialogue around cell therapy’s benefits against its potential risks. A further understanding of this balance is emerging, fueled by pioneering effort in this significant field of oncology research.
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